U1 snRNP Telescripting: Suppression of Premature Transcription Termination in Introns as a New Layer of Gene Regulation

Recent observations showed that nascent RNA polymerase II transcripts, pre-mRNAs, and noncoding RNAs are highly susceptible to premature 3'-end cleavage and polyadenylation (PCPA) from numerous intronic cryptic polyadenylation signals (PASs). The importance of this in gene regulation was not pr...

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Published inCold Spring Harbor perspectives in biology Vol. 11; no. 2; p. a032235
Main Authors Venters, Christopher C, Oh, Jung-Min, Di, Chao, So, Byung Ran, Dreyfuss, Gideon
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.02.2019
Subjects
Animals
Antisense oligonucleotides
CONCEPT
Dependence
DNA-directed RNA polymerase
Elongation
Exons
Gene expression
Gene Expression Regulation - physiology
Gene regulation
Humans
Introns
Polyadenylation
Ribonucleic acid
Ribonucleoproteins (small nuclear)
Ribonucleoproteins, Small Nuclear - metabolism
RNA
RNA polymerase
RNA polymerase II
RNA, Small Nuclear - genetics
RNA, Small Nuclear - metabolism
snRNA
Splicing
Transcription elongation
Transcription termination
Transcription Termination, Genetic
Vertebrates
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Summary:Recent observations showed that nascent RNA polymerase II transcripts, pre-mRNAs, and noncoding RNAs are highly susceptible to premature 3'-end cleavage and polyadenylation (PCPA) from numerous intronic cryptic polyadenylation signals (PASs). The importance of this in gene regulation was not previously appreciated as PASs, despite their prevalence, were thought to be active in terminal exons at gene ends. Unexpectedly, antisense oligonucleotide interference with U1 snRNA base-pairing to 5' splice sites, which is necessary for U1 snRNP's (U1) function in splicing, caused widespread PCPA in metazoans. This uncovered U1's PCPA suppression activity, termed telescripting, as crucial for full-length transcription in thousands of vertebrate genes, providing a general role in transcription elongation control. Progressive intron-size expansion in metazoan evolution greatly increased PCPA vulnerability and dependence on U1 telescripting. We describe how these observations unfolded and discuss U1 telescripting's role in shaping the transcriptome.
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These authors contributed equally to this work.
ISSN:1943-0264
1943-0264
DOI:10.1101/cshperspect.a032235