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PMID: 19029310 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Deadenylation is a widespread effect of miRNA regulation.

RNA (New York, N.Y.) ·Vol. 15 ·No. 1 ·2009-01-00 ·Pages 21-32

Eulalio A, Huntzinger E, Nishihara T, Rehwinkel J, Fauser M, Izaurralde E

Abstract

miRNAs silence gene expression by repressing translation and/or by promoting mRNA decay. In animal cells, degradation of partially complementary miRNA targets occurs via deadenylation by the CAF1-CCR4-NOT1 deadenylase complex, followed by decapping and subsequent exonucleolytic digestion. To determine how generally miRNAs trigger deadenylation, we compared mRNA expression profiles in D. melanogaster cells depleted of AGO1, CAF1, or NOT1. We show that approximately 60% of AGO1 targets are regulated by CAF1 and/or NOT1, indicating that deadenylation is a widespread effect of miRNA regulation. However, neither a poly(A) tail nor mRNA circularization are required for silencing, because mRNAs whose 3' ends are generated by a self-cleaving ribozyme are also silenced in vivo. We show further that miRNAs trigger mRNA degradation, even when binding by 40S ribosomal subunits is inhibited in cis. These results indicate that miRNAs promote mRNA decay by altering mRNP composition and/or conformation, rather than by directly interfering with the binding and function of ribosomal subunits.

MeSH Terms
Animals Argonaute Proteins Cells, Cultured Chromosomal Proteins, Non-Histone/genetics,metabolism Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,metabolism Eukaryotic Initiation Factors Gene Silencing MicroRNAs/genetics,metabolism Molecular Chaperones/genetics,metabolism Poly A/genetics,metabolism Protein Biosynthesis RNA Stability/genetics,physiology RNA, Messenger/genetics,metabolism Retinoblastoma-Binding Protein 4 Ribonucleases/genetics,metabolism Ribonucleoproteins/metabolism
Chemicals
AGO1 protein, Drosophila Argonaute Proteins Caf1-55 protein, Drosophila Chromosomal Proteins, Non-Histone Drosophila Proteins Eukaryotic Initiation Factors MicroRNAs Molecular Chaperones RNA, Messenger Retinoblastoma-Binding Protein 4 Ribonucleoproteins messenger ribonucleoprotein Poly A CCR4 protein, Drosophila Ribonucleases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Eulalio Ana
Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany.
Huntzinger Eric
Nishihara Tadashi
Rehwinkel Jan
Fauser Maria
Izaurralde Elisa
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
DOI
10.1261/rna.1399509
Published
2009-01-00
Epub
2008-00-24
Pages
21-32
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC2612776
Subset
IM
External Links
PubMed source DOI: 10.1261/rna.1399509 PMC Full Text View journal details
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