Wilusz, J. E., Jnbaptiste, C. K., Lu, L. Y., Kuhn, C. D., Joshua-Tor, L., Sharp, P. A. (November 2012) A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails. Genes Dev, 26 (21). pp. 2392-407. ISSN 1549-5477 (Electronic)0890-9369 (Linking)
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Abstract
The MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA. Despite being transcribed by RNA polymerase II, the 3' end of MALAT1 is produced not by canonical cleavage/polyadenylation but instead by recognition and cleavage of a tRNA-like structure by RNase P. Mature MALAT1 thus lacks a poly(A) tail yet is expressed at a level higher than many protein-coding genes in vivo. Here we show that the 3' ends of MALAT1 and the MEN beta long noncoding RNAs are protected from 3'-5' exonucleases by highly conserved triple helical structures. Surprisingly, when these structures are placed downstream from an ORF, the transcript is efficiently translated in vivo despite the lack of a poly(A) tail. The triple helix therefore also functions as a translational enhancer, and mutations in this region separate this translation activity from simple effects on RNA stability or transport. We further found that a transcript ending in a triple helix is efficiently repressed by microRNAs in vivo, arguing against a major role for the poly(A) tail in microRNA-mediated silencing. These results provide new insights into how transcripts that lack poly(A) tails are stabilized and regulated and suggest that RNA triple-helical structures likely have key regulatory functions in vivo.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > analysis and processing bioinformatics > genomics and proteomics > analysis and processing > DNA RNA Processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA regulation |
| CSHL Authors: | |
| Communities: | CSHL Post Doctoral Fellows CSHL labs > Joshua-Tor lab CSHL Cancer Center Program > Gene Regulation and Cell Proliferation |
| Depositing User: | Matt Covey |
| Date: | 1 November 2012 |
| Date Deposited: | 17 Jan 2013 19:46 |
| Last Modified: | 03 Nov 2017 20:00 |
| PMCID: | PMC3489998 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27080 |
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