期刊
RNA
卷 24, 期 6, 页码 778-786出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.064899.117
关键词
MAT2A; S-adenosylmethionine; intron detention; intron retention; splicing
资金
- American Cancer Society [RSG-14-064-01-RMC]
- Welch Foundation [I-1915-20170325]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health [R01AI123165]
- National Institutes of Health [T32GM007062]
Transcriptome analysis of human cells has revealed that intron retention controls the expression of a large number of genes with diverse cellular functions. Detained introns (DI) constitute a subgroup of transcripts with retained introns that are not exported to the cytoplasm but instead remain in the nucleus. Previous studies reported that the splicing of DIs in the CLK1 transcript is post-transcriptionally induced to produce mature mRNA in the absence of new transcription. Thus, CLK1-DI serves as a precursor or reservoir for the CLK1 mRNA. However, whether this is a universal mechanism for gene regulation by intron detention remains unknown. The MAT2A gene encodes S-adenosylmethionine (SAM) synthetase and it contains a DI that is regulated in response to intracellular SAM levels. We used three independent assays to assess the precursor-product relationship between MAT2A-DI and MAT2A mRNA. In contrast to CLK1-DI, these data support a model in which the MAT2A-DI transcript is not a precursor to mRNA but is instead a dead-end RNA fated for nuclear decay. Additionally, we show that in SAM-deprived conditions the cotranscriptional splicing of MAT2A detained introns increases. We conclude that polyadenylated RNAs with Dls can have at least two distinct fates. They can serve as nuclear reservoirs of pre-mRNAs available for rapid induction by the cell, or they constitute dead-end RNAs that are degraded in the nucleus.
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