Abstract
We have made a detailed molecular analysis of the reactions leading to the formation of mature 3' ends in mammalian histone mRNAs. Using two analytical protocols we have identified an essential sequence motif in the downstream spacer which is consistently present, albeit in diffuse form, mammalian histone genes. Tampering with this sequence element completely abolishes 3' processing. However, 3' cleavage in vitro, although at a very much reduced rate, can be detected when the conserved hairpin is deleted from histone precursor mRNAs. U7 snRNA, previously shown to be essential for the maturation of sea urchin histone messages, was isolated from murine cells and the sequence was determined. The approximately 63-nucleotide, trimethyl-G-capped, murine U7 snRNA possesses a sequence shown in the sea urchin U7 to be required for Sm-precipitability, and like the sea urchin U7, the 3' end of murine U7 is encased in a hairpin structure. The 5' sequence of murine U7 exhibits extensive sequence complementarity to the conserved downstream motif of the histone precursor. As expected, oligo-nucleotide-directed RNase H cleavage of this portion of murine U7 inhibits the in vitro processing reaction. These experiments identify a set of specific contacts between mammalian U7 and histone precursor RNA which is indispensable for the maturation reaction.
MeSH Terms
Animals
Base Sequence
DNA/metabolism
Histones/genetics,metabolism
In Vitro Techniques
Mice
Molecular Conformation
RNA Precursors/metabolism
RNA Processing, Post-Transcriptional
RNA, Small Nuclear/metabolism
Sea Urchins
Sequence Homology, Nucleic Acid
Chemicals
Histones
RNA Precursors
RNA, Small Nuclear
DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cotten M
Research Institute of Molecular Pathology, Vienna, Austria.
Gick O
Vasserot A
Schaffner G
Birnstiel M L
References (30)
30 references, click to expand
-
Direct chemical method for sequencing RNA.
Proc Natl Acad Sci U S A. 1979 Apr;76(4):1760-4
PMID: 377283
-
Heat-labile regulatory factor is required for 3' processing of histone precursor mRNAs.
Proc Natl Acad Sci U S A. 1987 Dec;84(24):8937-40
PMID: 2962194
-
Specific labeling of 3' termini of RNA with T4 RNA ligase.
Methods Enzymol. 1980;65(1):65-74
PMID: 6154874
-
The organization and expression of histone gene families.
Cell. 1981 Aug;25(2):301-13
PMID: 6793234
-
Generation of authentic 3' termini of an H2A mRNA in vivo is dependent on a short inverted DNA repeat and on spacer sequences.
Cell. 1982 Apr;28(4):739-45
PMID: 6284372
-
Human beta-globin pre-mRNA synthesized in vitro is accurately spliced in Xenopus oocyte nuclei.
Cell. 1983 Mar;32(3):681-94
PMID: 6550524
-
Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle.
Mol Cell Biol. 1983 Apr;3(4):539-50
PMID: 6406835
-
Nucleotide sequences of H1 histone genes from Xenopus laevis. A recently diverged pair of H1 genes and an unusual H1 pseudogene.
Nucleic Acids Res. 1983 Jun 25;11(12):4093-107
PMID: 6866767
-
The terminal RNA stem-loop structure and 80 bp of spacer DNA are required for the formation of 3' termini of sea urchin H2A mRNA.
Cell. 1983 Dec;35(2 Pt 1):433-40
PMID: 6317188
-
3' editing of mRNAs: sequence requirements and involvement of a 60-nucleotide RNA in maturation of histone mRNA precursors.
Proc Natl Acad Sci U S A. 1984 Feb;81(4):1057-61
PMID: 6583695
-
The 5' terminus of the RNA moiety of U1 small nuclear ribonucleoprotein particles is required for the splicing of messenger RNA precursors.
Cell. 1984 Aug;38(1):299-307
PMID: 6235919
-
Processing and nucleo-cytoplasmic transport of histone gene transcripts.
Nucleic Acids Res. 1984 Nov 26;12(22):8539-51
PMID: 6095202
-
Nuclear segregation of U2 snRNA requires binding of specific snRNP proteins.
Cell. 1985 Jan;40(1):111-8
PMID: 2578319
-
The cDNA sequences of the sea urchin U7 small nuclear RNA suggest specific contacts between histone mRNA precursor and U7 RNA during RNA processing.
EMBO J. 1984 Dec 1;3(12):2801-7
PMID: 6084590
-
Transcription termination and 3' processing: the end is in site!
Cell. 1985 Jun;41(2):349-59
PMID: 2580642
-
Faithful cell-cycle regulation of a recombinant mouse histone H4 gene is controlled by sequences in the 3'-terminal part of the gene.
Proc Natl Acad Sci U S A. 1985 Jul;82(13):4389-93
PMID: 3925455
-
The conserved CAAGAAAGA spacer sequence is an essential element for the formation of 3' termini of the sea urchin H3 histone mRNA by RNA processing.
EMBO J. 1985 Feb;4(2):481-9
PMID: 2410259
-
Analysis of a sea urchin gene cluster coding for the small nuclear U7 RNA, a rare RNA species implicated in the 3' editing of histone precursor mRNAs.
Proc Natl Acad Sci U S A. 1986 May;83(10):3243-7
PMID: 3458178
-
Generation of histone mRNA 3' ends by endonucleolytic cleavage of the pre-mRNA in a snRNP-dependent in vitro reaction.
EMBO J. 1986 Jun;5(6):1319-26
PMID: 3015597
-
Genetic complementation in the Xenopus oocyte: co-expression of sea urchin histone and U7 RNAs restores 3' processing of H3 pre-mRNA in the oocyte.
EMBO J. 1986 Jul;5(7):1675-82
PMID: 2943587
-
A compensatory base change in U1 snRNA suppresses a 5' splice site mutation.
Cell. 1986 Sep 12;46(6):827-35
PMID: 3757028
-
Compensatory mutations suggest that base-pairing with a small nuclear RNA is required to form the 3' end of H3 messenger RNA.
Nature. 1986 Oct 30-Nov 5;323(6091):777-81
PMID: 3022153
-
Translation is required for regulation of histone mRNA degradation.
Cell. 1987 Feb 27;48(4):615-26
PMID: 3028643
-
A signal regulating mouse histone H4 mRNA levels in a mammalian cell cycle mutant and sequences controlling RNA 3' processing are both contained within the same 80-bp fragment.
EMBO J. 1986 Dec 1;5(12):3297-303
PMID: 3816761
-
5' cleavage site in eukaryotic pre-mRNA splicing is determined by the overall 5' splice region, not by the conserved 5' GU.
Cell. 1987 Jul 17;50(2):237-46
PMID: 3647844
-
Both conserved signals on mammalian histone pre-mRNAs associate with small nuclear ribonucleoproteins during 3' end formation in vitro.
Mol Cell Biol. 1987 May;7(5):1663-72
PMID: 2955216
-
RNA 3' processing regulates histone mRNA levels in a mammalian cell cycle mutant. A processing factor becomes limiting in G1-arrested cells.
EMBO J. 1987 Jun;6(6):1721-6
PMID: 3608992
-
Sequences controlling histone H4 mRNA abundance.
EMBO J. 1987 Jun;6(6):1825-31
PMID: 3608993
-
The inability of the Psammechinus miliaris H3 RNA to be processed in the Xenopus oocyte is associated with sequences distinct from those highly conserved amongst sea urchin histone RNAs.
Nucleic Acids Res. 1987 Oct 26;15(20):8305-17
PMID: 2823227
-
A regulatory sequence near the 3' end of sea urchin histone genes.
Nucleic Acids Res. 1979 Jul 11;6(9):2997-3008
PMID: 493132