A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails

Wilusz, J. E., Jnbaptiste, C. K., Lu, L. Y., Kuhn, C. D., Joshua-Tor, L., Sharp, P. A. (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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/23073843
DOI: 10.1101/gad.204438.112

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 Deposited: 17 Jan 2013 19:46
Last Modified: 13 Oct 2015 18:43
PMCID: PMC3489998
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27080

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving