U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation

In eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockd...

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Bibliographic Details
Published in:Nature (London) 2010-12, Vol.468 (7324), p.664-668
Main Authors: Dreyfuss, Gideon, Kaida, Daisuke, Berg, Michael G, Younis, Ihab, Kasim, Mumtaz, Singh, Larry N, Wan, Lili
Format: Article
Language:English
Subjects:
631/337/1645/1792
631/45/612/1230
Base Pairing
Base Sequence
Cellular biology
Eukaryotes
Gene expression
Genetic aspects
Genomics
HeLa Cells
Humanities and Social Sciences
Humans
Introns - genetics
Messenger RNA
Molecular Sequence Data
multidisciplinary
Oligonucleotide Array Sequence Analysis
Oligonucleotides, Antisense - genetics
Oligonucleotides, Antisense - metabolism
Oligonucleotides, Antisense - pharmacology
Physiological aspects
Polyadenylation - drug effects
Polyadenylation - genetics
Pyrans - pharmacology
Ribonucleic acid
Ribonucleoprotein, U1 Small Nuclear - antagonists & inhibitors
Ribonucleoprotein, U1 Small Nuclear - genetics
Ribonucleoprotein, U1 Small Nuclear - metabolism
Ribonucleoproteins
RNA
RNA Precursors - genetics
RNA Precursors - metabolism
RNA splicing
RNA Splicing - drug effects
RNA Splicing - genetics
RNA, Small Nuclear - genetics
RNA, Small Nuclear - metabolism
Science
Science (multidisciplinary)
Spiro Compounds - pharmacology
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Summary:In eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockdown in HeLa cells, and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. In addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation in numerous pre-mRNAs at cryptic polyadenylation signals, frequently in introns near (
ISSN:0028-0836
1476-4687
DOI:10.1038/nature09479