Home LiteratureArticle Details
PMID: 20019688 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

RNA processing and its regulation: global insights into biological networks.

Nature reviews. Genetics ·Vol. 11 ·No. 1 ·2010-01-00 ·Pages 75-87

Licatalosi DD, Darnell RB

Abstract

In recent years views of eukaryotic gene expression have been transformed by the finding that enormous diversity can be generated at the RNA level. Advances in technologies for characterizing RNA populations are revealing increasingly complete descriptions of RNA regulation and complexity; for example, through alternative splicing, alternative polyadenylation and RNA editing. New biochemical strategies to map protein-RNA interactions in vivo are yielding transcriptome-wide insights into mechanisms of RNA processing. These advances, combined with bioinformatics and genetic validation, are leading to the generation of functional RNA maps that reveal the rules underlying RNA regulation and networks of biologically coherent transcripts. Together these are providing new insights into molecular cell biology and disease.

MeSH Terms
Alternative Splicing Animals Computational Biology/methods Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Genetic Variation Humans Models, Biological Models, Genetic Oligonucleotide Array Sequence Analysis Polyadenylation RNA/genetics RNA Editing Transcription, Genetic
Chemicals
RNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Licatalosi Donny D
Howard Hughes Medical Institute, Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York 10021, USA.
Darnell Robert B
References (162)
162 references, click to expand
  1. Multiple and specific mRNA processing targets for the major human hnRNP proteins.
    Mol Cell Biol. 2008 Oct;28(19):6033-43 PMID: 18644864
  2. Mechanisms and cellular roles of local protein synthesis in mammalian cells.
    Curr Opin Cell Biol. 2008 Apr;20(2):144-9 PMID: 18378131
  3. CLIP: construction of cDNA libraries for high-throughput sequencing from RNAs cross-linked to proteins in vivo.
    Methods. 2009 Jul;48(3):287-93 PMID: 19272451
  4. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
    Science. 1994 Sep 16;265(5179):1706-9 PMID: 8085156
  5. Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay.
    Genes Dev. 2007 Mar 15;21(6):708-18 PMID: 17369403
  6. Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2.
    Genes Dev. 2008 Sep 15;22(18):2550-63 PMID: 18794351
  7. Cellular stress and RNA splicing.
    Trends Biochem Sci. 2009 Mar;34(3):146-53 PMID: 19208481
  8. Global analysis of alternative splicing differences between humans and chimpanzees.
    Genes Dev. 2007 Nov 15;21(22):2963-75 PMID: 17978102
  9. Multiplex amplification of large sets of human exons.
    Nat Methods. 2007 Nov;4(11):931-6 PMID: 17934468
  10. Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing.
    Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3513-8 PMID: 19221030
  11. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing.
    Nat Genet. 2008 Dec;40(12):1413-5 PMID: 18978789
  12. Origins and Mechanisms of miRNAs and siRNAs.
    Cell. 2009 Feb 20;136(4):642-55 PMID: 19239886
  13. Characterization of heterogeneous nuclear RNA-protein complexes in vivo with monoclonal antibodies.
    Mol Cell Biol. 1984 Jun;4(6):1104-14 PMID: 6204191
  14. Split genes and RNA splicing.
    Science. 1979 Apr 20;204(4390):264-71 PMID: 373120
  15. Noncoding RNAs of the H/ACA family.
    Cold Spring Harb Symp Quant Biol. 2006;71:395-405 PMID: 17381322
  16. The end of the message--another link between yeast and mammals.
    Science. 1996 Nov 29;274(5292):1481-2 PMID: 8966619
  17. Neuronal regulation of alternative pre-mRNA splicing.
    Nat Rev Neurosci. 2007 Nov;8(11):819-31 PMID: 17895907
  18. Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system.
    PLoS Biol. 2008 Oct 28;6(10):e255 PMID: 18959479
  19. A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6350-5 PMID: 10829067
  20. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability.
    Neuron. 2000 Feb;25(2):359-71 PMID: 10719891
  21. Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay.
    Mol Cell Biol. 2008 Jul;28(13):4320-30 PMID: 18443041
  22. 3' non-coding region sequences in eukaryotic messenger RNA.
    Nature. 1976 Sep 16;263(5574):211-4 PMID: 822353
  23. RNA-specific ribonucleotidyl transferases.
    RNA. 2007 Nov;13(11):1834-49 PMID: 17872511
  24. Genome-wide detection of tissue-specific alternative splicing in the human transcriptome.
    Nucleic Acids Res. 2002 Sep 1;30(17):3754-66 PMID: 12202761
  25. Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts.
    Genome Res. 2009 Mar;19(3):381-94 PMID: 19116412
  26. The gene encoding the splicing factor SF2/ASF is a proto-oncogene.
    Nat Struct Mol Biol. 2007 Mar;14(3):185-93 PMID: 17310252
  27. The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a.
    Nat Struct Mol Biol. 2007 Jul;14(7):591-6 PMID: 17558416
  28. The centrality of RNA.
    Cell. 2009 Feb 20;136(4):577-80 PMID: 19239877
  29. Site-specific crosslinking of human microRNPs to RNA targets.
    RNA. 2008 Oct;14(10):2254-9 PMID: 18719246
  30. HITS-CLIP yields genome-wide insights into brain alternative RNA processing.
    Nature. 2008 Nov 27;456(7221):464-9 PMID: 18978773
  31. mRNA localization: gene expression in the spatial dimension.
    Cell. 2009 Feb 20;136(4):719-30 PMID: 19239891
  32. RNA editing by adenosine deaminases that act on RNA.
    Annu Rev Biochem. 2002;71:817-46 PMID: 12045112
  33. Specific and non-specific mammalian RNA terminal uridylyl transferases.
    Biochim Biophys Acta. 2008 Apr;1779(4):281-5 PMID: 18067875
  34. A translational profiling approach for the molecular characterization of CNS cell types.
    Cell. 2008 Nov 14;135(4):738-48 PMID: 19013281
  35. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps.
    Nature. 2009 Jul 23;460(7254):479-86 PMID: 19536157
  36. Genome-wide transcription and the implications for genomic organization.
    Nat Rev Genet. 2007 Jun;8(6):413-23 PMID: 17486121
  37. Application of a translational profiling approach for the comparative analysis of CNS cell types.
    Cell. 2008 Nov 14;135(4):749-62 PMID: 19013282
  38. CLIP identifies Nova-regulated RNA networks in the brain.
    Science. 2003 Nov 14;302(5648):1212-5 PMID: 14615540
  39. "Cotranscriptionality": the transcription elongation complex as a nexus for nuclear transactions.
    Mol Cell. 2009 Oct 23;36(2):178-91 PMID: 19854129
  40. Identification and analysis of alternative splicing events conserved in human and mouse.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2850-5 PMID: 15708978
  41. Long non-coding RNAs: insights into functions.
    Nat Rev Genet. 2009 Mar;10(3):155-9 PMID: 19188922
  42. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45 PMID: 10357856
  43. Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation.
    RNA. 2005 Oct;11(10):1485-93 PMID: 16131587
  44. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.
    Nature. 1982 Jul 15;298(5871):240-4 PMID: 6283379
  45. An extensive network of coupling among gene expression machines.
    Nature. 2002 Apr 4;416(6880):499-506 PMID: 11932736
  46. Rethinking ALS: the FUS about TDP-43.
    Cell. 2009 Mar 20;136(6):1001-4 PMID: 19303844
  47. Implications of RNA-RNA splicing in evolution of eukaryotic cells.
    Science. 1978 Dec 22;202(4374):1257-60 PMID: 364651
  48. Nova autoregulation reveals dual functions in neuronal splicing.
    EMBO J. 2005 Apr 20;24(8):1608-20 PMID: 15933722
  49. An RNA map predicting Nova-dependent splicing regulation.
    Nature. 2006 Nov 30;444(7119):580-6 PMID: 17065982
  50. Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements.
    Nature. 2007 Apr 19;446(7138):926-9 PMID: 17361132
  51. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4).
    Am J Hum Genet. 2004 Jun;74(6):1128-35 PMID: 15106121
  52. SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart.
    Dev Cell. 2009 Apr;16(4):528-38 PMID: 19386262
  53. Splicing regulation in neurologic disease.
    Neuron. 2006 Oct 5;52(1):93-101 PMID: 17015229
  54. Divergent transcription: a new feature of active promoters.
    Cell Cycle. 2009 Aug 15;8(16):2557-64 PMID: 19597342
  55. Global analysis of mRNA splicing.
    RNA. 2008 Feb;14(2):197-203 PMID: 18083834
  56. Alternative splicing and protein structure evolution.
    Nucleic Acids Res. 2008 Feb;36(2):550-8 PMID: 18055499
  57. The turnover of nuclear DNA-like RNA in HeLa cells.
    J Cell Biol. 1968 Oct;39(1):112-8 PMID: 5678443
  58. Crawling out of the RNA world.
    Cell. 2009 Feb 20;136(4):599-602 PMID: 19239881
  59. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites.
    Cell. 1990 Jul 13;62(1):35-42 PMID: 2364434
  60. Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses.
    RNA. 2004 Nov;10(11):1692-4 PMID: 15388877
  61. Why genes in pieces?
    Nature. 1978 Feb 9;271(5645):501 PMID: 622185
  62. Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer.
    Mol Cell Biol. 2003 Jul;23(13):4687-700 PMID: 12808107
  63. A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing.
    Nucleic Acids Res. 2007;35(14):4845-57 PMID: 17626050
  64. N6-adenosine methylation in mRNA: substrate specificity and enzyme complexity.
    Biochimie. 1994;76(12):1109-14 PMID: 7748945
  65. Biased alternative polyadenylation in human tissues.
    Genome Biol. 2005;6(12):R100 PMID: 16356263
  66. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling.
    Science. 2009 Apr 10;324(5924):218-23 PMID: 19213877
  67. Cross-linking of mRNA to proteins by irradiation of intact cells with ultraviolet light.
    Eur J Biochem. 1980 Nov;112(2):323-30 PMID: 7460925
  68. Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments.
    Trends Genet. 2005 Feb;21(2):93-102 PMID: 15661355
  69. Current-generation high-throughput sequencing: deepening insights into mammalian transcriptomes.
    Genes Dev. 2009 Jun 15;23(12):1379-86 PMID: 19528315
  70. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing.
    Science. 2009 May 29;324(5931):1210-3 PMID: 19478186
  71. Alternative isoform regulation in human tissue transcriptomes.
    Nature. 2008 Nov 27;456(7221):470-6 PMID: 18978772
  72. Protein factors in pre-mRNA 3'-end processing.
    Cell Mol Life Sci. 2008 Apr;65(7-8):1099-122 PMID: 18158581
  73. Regulation of translation initiation in eukaryotes: mechanisms and biological targets.
    Cell. 2009 Feb 20;136(4):731-45 PMID: 19239892
  74. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.
    Mol Cell. 2007 Aug 3;27(3):435-48 PMID: 17679093
  75. Ovalbumin gene is split in chicken DNA.
    Nature. 1977 Nov 24;270(5635):314-9 PMID: 593351
  76. A systematic analysis of intronic sequences downstream of 5' splice sites reveals a widespread role for U-rich motifs and TIA1/TIAL1 proteins in alternative splicing regulation.
    Genome Res. 2008 Aug;18(8):1247-58 PMID: 18456862
  77. Photo-induced joining of a transfer RNA with its cognate aminoacyl-transfer RNA synthetase.
    J Mol Biol. 1974 Apr 25;84(4):503-13 PMID: 4840999
  78. How did alternative splicing evolve?
    Nat Rev Genet. 2004 Oct;5(10):773-82 PMID: 15510168
  79. Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines.
    Nat Genet. 2008 Dec;40(12):1416-25 PMID: 18978788
  80. ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle.
    Cell. 2005 Jan 14;120(1):59-72 PMID: 15652482
  81. Dscam-mediated cell recognition regulates neural circuit formation.
    Annu Rev Cell Dev Biol. 2008;24:597-620 PMID: 18837673
  82. RNA and disease.
    Cell. 2009 Feb 20;136(4):777-93 PMID: 19239895
  83. Breaking the code of polyadenylation-induced translation.
    Cell. 2008 Feb 8;132(3):335-7 PMID: 18267064
  84. Dynamic regulation of alternative splicing by silencers that modulate 5' splice site competition.
    Cell. 2008 Dec 26;135(7):1224-36 PMID: 19109894
  85. Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein.
    Cell. 2009 Sep 4;138(5):898-910 PMID: 19737518
  86. Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells.
    Curr Opin Cell Biol. 2005 Jun;17(3):309-15 PMID: 15901502
  87. The spliceosome: design principles of a dynamic RNP machine.
    Cell. 2009 Feb 20;136(4):701-18 PMID: 19239890
  88. A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart.
    Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20333-8 PMID: 19075228
  89. RNA-Seq: a revolutionary tool for transcriptomics.
    Nat Rev Genet. 2009 Jan;10(1):57-63 PMID: 19015660
  90. Small RNAs as guardians of the genome.
    Cell. 2009 Feb 20;136(4):656-68 PMID: 19239887
  91. Neurexins: three genes and 1001 products.
    Trends Genet. 1998 Jan;14(1):20-6 PMID: 9448462
  92. Alternative polyadenylation: a twist on mRNA 3' end formation.
    ACS Chem Biol. 2008 Oct 17;3(10):609-17 PMID: 18817380
  93. Pre-mRNA processing reaches back to transcription and ahead to translation.
    Cell. 2009 Feb 20;136(4):688-700 PMID: 19239889
  94. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids.
    Cell. 1977 Nov;12(3):721-32 PMID: 922889
  95. Structure of nuclear ribonucleoprotein: identification of proteins in contact with poly(A)+ heterogeneous nuclear RNA in living HeLa cells.
    J Cell Biol. 1981 Aug;90(2):380-4 PMID: 6169730
  96. Mechanisms of RNA-mediated disease.
    J Biol Chem. 2009 Mar 20;284(12):7419-23 PMID: 18957432
  97. A hierarchy of Hu RNA binding proteins in developing and adult neurons.
    J Neurosci. 1997 May 1;17(9):3024-37 PMID: 9096138
  98. Alternative translation start sites and hidden coding potential of eukaryotic mRNAs.
    Bioessays. 2008 Jul;30(7):683-91 PMID: 18536038
  99. RNA regulons: coordination of post-transcriptional events.
    Nat Rev Genet. 2007 Jul;8(7):533-43 PMID: 17572691
  100. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.
    Science. 2003 Dec 19;302(5653):2141-4 PMID: 14684825
  101. A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8306-10 PMID: 3479794
  102. RNA binding proteins and the regulation of neuronal synaptic plasticity.
    Curr Opin Neurobiol. 2006 Feb;16(1):102-10 PMID: 16418001
  103. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  104. Immunoglobulin RNA rearrangements in B lymphocyte differentiation.
    Adv Immunol. 1984;35:39-59 PMID: 6431764
  105. CLIP: a method for identifying protein-RNA interaction sites in living cells.
    Methods. 2005 Dec;37(4):376-86 PMID: 16314267
  106. Intronic sequences flanking alternatively spliced exons are conserved between human and mouse.
    Genome Res. 2003 Jul;13(7):1631-7 PMID: 12840041
  107. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
    Nat Rev Genet. 2008 Feb;9(2):102-14 PMID: 18197166
  108. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro.
    Cell. 1990 Jul 13;62(1):25-34 PMID: 2163768
  109. Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay.
    Mol Cell. 2004 Jan 16;13(1):91-100 PMID: 14731397
  110. Splicing in disease: disruption of the splicing code and the decoding machinery.
    Nat Rev Genet. 2007 Oct;8(10):749-61 PMID: 17726481
  111. Developing global insight into RNA regulation.
    Cold Spring Harb Symp Quant Biol. 2006;71:321-7 PMID: 17381312
  112. Making synaptic plasticity and memory last: mechanisms of translational regulation.
    Genes Dev. 2009 Jan 1;23(1):1-11 PMID: 19136621
  113. An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.
    Nat Struct Mol Biol. 2009 Feb;16(2):130-7 PMID: 19136955
  114. A regulator of Dscam mutually exclusive splicing fidelity.
    Nat Struct Mol Biol. 2007 Dec;14(12):1134-40 PMID: 21188797
  115. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription.
    Nature. 2008 Jul 3;454(7200):126-30 PMID: 18509338
  116. Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator.
    Nat Struct Mol Biol. 2008 Oct;15(10):1040-8 PMID: 18794844
  117. Genome-wide analysis of alternative pre-mRNA splicing and RNA-binding specificities of the Drosophila hnRNP A/B family members.
    Mol Cell. 2009 Feb 27;33(4):438-49 PMID: 19250905
  118. Alternative pre-mRNA splicing and proteome expansion in metazoans.
    Nature. 2002 Jul 11;418(6894):236-43 PMID: 12110900
  119. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code.
    RNA. 2008 May;14(5):802-13 PMID: 18369186
  120. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.
    Mol Cell Biol. 2000 Oct;20(20):7463-79 PMID: 11003644
  121. Structure of nuclear ribonucleoprotein: heterogeneous nuclear RNA is complexed with a major sextet of proteins in vivo.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1599-602 PMID: 6572923
  122. Evolution of Nova-dependent splicing regulation in the brain.
    PLoS Genet. 2007 Oct;3(10):1838-47 PMID: 17937501
  123. Muscleblind isoforms are functionally distinct and regulate alpha-actinin splicing.
    Differentiation. 2007 Jun;75(5):427-40 PMID: 17309604
  124. An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA.
    Cell. 1977 Sep;12(1):1-8 PMID: 902310
  125. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1.
    Mol Cell. 2007 Aug 3;27(3):420-34 PMID: 17679092
  126. Promoter usage and alternative splicing.
    Curr Opin Cell Biol. 2005 Jun;17(3):262-8 PMID: 15901495
  127. Large-scale transcriptional activity in chromosomes 21 and 22.
    Science. 2002 May 3;296(5569):916-9 PMID: 11988577
  128. Evolution and functions of long noncoding RNAs.
    Cell. 2009 Feb 20;136(4):629-41 PMID: 19239885
  129. Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1.
    Nat Genet. 2001 Sep;29(1):75-7 PMID: 11528396
  130. A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins.
    Neuron. 2005 Oct 20;48(2):229-36 PMID: 16242404
  131. Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):189-92 PMID: 12502788
  132. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.
    Cell. 2009 Aug 21;138(4):673-84 PMID: 19703394
  133. Are snRNPs involved in splicing?
    Nature. 1980 Jan 10;283(5743):220-4 PMID: 7350545
  134. Temporal requirement of the alternative-splicing factor Sfrs1 for the survival of retinal neurons.
    Development. 2008 Dec;135(23):3923-33 PMID: 18987029
  135. Transcriptional scaffolds for heterochromatin assembly.
    Cell. 2009 Feb 20;136(4):610-4 PMID: 19239883
  136. Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14085-90 PMID: 11121017
  137. The functional consequences of alternative promoter use in mammalian genomes.
    Trends Genet. 2008 Apr;24(4):167-77 PMID: 18329129
  138. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
    Nature. 2009 Mar 12;458(7235):223-7 PMID: 19182780
  139. Demonstration of an unstable RNA and of a precursor to ribosomal RNA in HeLa cells.
    Proc Natl Acad Sci U S A. 1963 Feb 15;49:240-8 PMID: 13991616
  140. Cancer-associated regulation of alternative splicing.
    Nat Struct Mol Biol. 2009 Jun;16(6):670-6 PMID: 19448617
  141. Paraneoplastic syndromes involving the nervous system.
    N Engl J Med. 2003 Oct 16;349(16):1543-54 PMID: 14561798
  142. Posttranscriptional regulation of miRNAs harboring conserved terminal loops.
    Mol Cell. 2008 Nov 7;32(3):383-93 PMID: 18995836
  143. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons.
    Genes Dev. 2007 Jul 1;21(13):1636-52 PMID: 17606642
  144. FMRP RNA targets: identification and validation.
    Genes Brain Behav. 2005 Aug;4(6):341-9 PMID: 16098133
  145. The intervening sequence RNA of Tetrahymena is an enzyme.
    Science. 1986 Jan 31;231(4737):470-5 PMID: 3941911
  146. Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene.
    Proc Natl Acad Sci U S A. 1978 Feb;75(2):725-9 PMID: 273235
  147. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.
    Am J Hum Genet. 2003 May;72(5):1293-9 PMID: 12690580
  148. The many pathways of RNA degradation.
    Cell. 2009 Feb 20;136(4):763-76 PMID: 19239894
  149. Discovery of tissue-specific exons using comprehensive human exon microarrays.
    Genome Biol. 2007;8(4):R64 PMID: 17456239
  150. Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition.
    Cell. 2005 Oct 7;123(1):105-18 PMID: 16213216
  151. Nova regulates brain-specific splicing to shape the synapse.
    Nat Genet. 2005 Aug;37(8):844-52 PMID: 16041372
  152. The emerging role of splicing factors in cancer.
    EMBO Rep. 2008 Nov;9(11):1087-93 PMID: 18846105
  153. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches.
    Nat Rev Mol Cell Biol. 2009 Nov;10(11):741-54 PMID: 19773805
  154. Understanding alternative splicing: towards a cellular code.
    Nat Rev Mol Cell Biol. 2005 May;6(5):386-98 PMID: 15956978
  155. Functional coordination of alternative splicing in the mammalian central nervous system.
    Genome Biol. 2007;8(6):R108 PMID: 17565696
  156. mRNA-Seq whole-transcriptome analysis of a single cell.
    Nat Methods. 2009 May;6(5):377-82 PMID: 19349980
  157. Spliced segments at the 5' terminus of adenovirus 2 late mRNA.
    Proc Natl Acad Sci U S A. 1977 Aug;74(8):3171-5 PMID: 269380
  158. CLIP: crosslinking and immunoprecipitation of in vivo RNA targets of RNA-binding proteins.
    Methods Mol Biol. 2008;488:85-98 PMID: 18982285
  159. Tissue-specific splicing factor gene expression signatures.
    Nucleic Acids Res. 2008 Sep;36(15):4823-32 PMID: 18653532
  160. Unusual intron conservation near tissue-regulated exons found by splicing microarrays.
    PLoS Comput Biol. 2006 Jan;2(1):e4 PMID: 16424921
  161. Splicing double: insights from the second spliceosome.
    Nat Rev Mol Cell Biol. 2003 Dec;4(12):960-70 PMID: 14685174
  162. Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites.
    Science. 2008 Jun 20;320(5883):1643-7 PMID: 18566288
Article Info
Journal
Nature reviews. Genetics
Abbr.
Nat Rev Genet
ISSN
1471-0064
DOI
10.1038/nrg2673
Published
2010-01-00
Pages
75-87
Language
English
Region
England
NLM ID
100962779
PMCID
PMC3229837
Subset
IM
Grants
NINDS NIH HHS · R01 NS034389 · United States
NINDS NIH HHS · R01 NS034389-15 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1038/nrg2673 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2