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PMID: 22770214 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

U1 snRNP determines mRNA length and regulates isoform expression.

Cell ·Vol. 150 ·No. 1 ·2012-07-06 ·Pages 53-64

Berg MG, Singh LN, Younis I, Liu Q, Pinto AM, Kaida D, Zhang Z, Cho S, Sherrill-Mix S, Wan L, Dreyfuss G

Abstract

U1 snRNP (U1), in addition to its splicing role, protects pre-mRNAs from drastic premature termination by cleavage and polyadenylation (PCPA) at cryptic polyadenylation signals (PASs) in introns. Here, a high-throughput sequencing strategy of differentially expressed transcripts (HIDE-seq) mapped PCPA sites genome wide in divergent organisms. Surprisingly, whereas U1 depletion terminated most nascent gene transcripts within ~1 kb, moderate functional U1 level decreases, insufficient to inhibit splicing, dose-dependently shifted PCPA downstream and elicited mRNA 3' UTR shortening and proximal 3' exon switching characteristic of activated immune and neuronal cells, stem cells, and cancer. Activated neurons' signature mRNA shortening could be recapitulated by U1 decrease and antagonized by U1 overexpression. Importantly, we show that rapid and transient transcriptional upregulation inherent to neuronal activation physiology creates U1 shortage relative to pre-mRNAs. Additional experiments suggest cotranscriptional PCPA counteracted by U1 association with nascent transcripts, a process we term telescripting, ensuring transcriptome integrity and regulating mRNA length.

MeSH Terms
Animals Cell Line Drosophila melanogaster Genome-Wide Association Study HeLa Cells High-Throughput Nucleotide Sequencing Humans Mice NIH 3T3 Cells Neurons/metabolism RNA 3' End Processing RNA Precursors/metabolism RNA Splicing Ribonucleoprotein, U1 Small Nuclear/metabolism
Chemicals
RNA Precursors Ribonucleoprotein, U1 Small Nuclear
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Berg Michael G
Howard Hughes Medical Institute, USA.
Singh Larry N
Younis Ihab
Liu Qiang
Pinto Anna Maria
Kaida Daisuke
Zhang Zhenxi
Cho Sungchan
Sherrill-Mix Scott
Wan Lili
Dreyfuss Gideon
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2012.05.029
Published
2012-07-06
Pages
53-64
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3412174
Subset
IM
Grants
Howard Hughes Medical Institute · United States
Corrections
CommentIn
PMID: 22770211
External Links
PubMed source DOI: 10.1016/j.cell.2012.05.029 PMC Full Text View journal details
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