U2 snRNP is required for expression of the 3' end of genes

Pre-mRNA in eukaryotes is subjected to mRNA processing, which includes capping, polyadenylation, and splicing. Transcription and mRNA processing are coupled, and this coupling stimulates mRNA processing; however, the effects of mRNA processing on transcription are not fully understood. In this study...

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Bibliographic Details
Published in:PloS one 2014-05, Vol.9 (5), p.e98015
Main Authors: Koga, Mitsunori, Satoh, Takayuki, Takasaki, Ichiro, Kawamura, Yumi, Yoshida, Minoru, Kaida, Daisuke
Format: Article
Language:English
Subjects:
3' Untranslated Regions
5' Untranslated Regions
Accumulation
Antisense oligonucleotides
Biology and life sciences
Cell Line
Culture media
Elongation
Epidermal growth factor receptors
Eukaryotes
Exosome Multienzyme Ribonuclease Complex - genetics
Gene expression
Gene Expression Regulation - drug effects
Gene Knockdown Techniques
Gene regulation
Genes
Genomes
HeLa Cells
Humans
Life sciences
Molecular biology
mRNA guanylyltransferase
mRNA processing
Polyadenylation
Proteins
Pyrans - pharmacology
Ribonucleoprotein, U2 Small Nuclear - metabolism
Ribonucleoproteins (small nuclear)
Ribonucleoproteins (U2 small nuclear)
RNA
RNA polymerase
RNA Polymerase II - metabolism
RNA Precursors - genetics
RNA Splicing - drug effects
RNA, Messenger - genetics
RNA-Binding Proteins - genetics
snRNA
Spiro Compounds - pharmacology
Splicing
Transcription elongation
Transcription, Genetic
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Summary:Pre-mRNA in eukaryotes is subjected to mRNA processing, which includes capping, polyadenylation, and splicing. Transcription and mRNA processing are coupled, and this coupling stimulates mRNA processing; however, the effects of mRNA processing on transcription are not fully understood. In this study, we found that inhibition of U2 snRNP by a splicing inhibitor, spliceostatin A (SSA), or by an antisense oligonucleotide to U2 snRNA, caused gene-specific 3'-end down-regulation. Removal of SSA from the culture media restored expression of the 3' ends of genes, suggesting that U2 snRNP is required for expression of the 3' end of genes. Finally, we found that SSA treatment caused accumulation of Pol II near the 5' end of 3'-end down regulated genes, such as CDK6, SMEK2 and EGFR, indicating that SSA treatment led to transcription elongation arrest on these genes. These findings suggest that U2 snRNP is important for production of full length mRNA probably through regulation of transcription elongation, and that a novel checkpoint mechanism prevents pre-mRNA from accumulating as a result of splicing deficiencies, and thereby prevents production of aberrant proteins that might be translated from pre-mRNAs through the arrest of transcription elongation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0098015