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

Title data

Wilusz, Jeremy E. ; JnBaptiste, Courtney K. ; Lu, Laura Y. ; Kuhn, Claus-D. ; Joshua-Tor, Leemor ; Sharp, Phillip A.:
A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails.
In: Genes & Development. Vol. 26 (2012) Issue 21 . - pp. 2392-2407.
ISSN 1549-5477
DOI: https://doi.org/10.1101/gad.204438.112

Official URL: Volltext

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: Amino Acid Motifs; Base Sequence; DNA Mutational Analysis; Gene Expression Regulation; HeLa Cells; Humans; MicroRNAs/metabolism; Molecular Sequence Data; Plasmids/genetics; Protein Denaturation; Protein Structure, Secondary; RNA 3' End Processing/genetics; RNA Stability; RNA, Long Noncoding/chemistry/*genetics/metabolism; RNA, Messenger/*genetics; Sequence Alignment
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Profile Fields > Advanced Fields > Molecular Biosciences
Research Institutions > Research Centres > Bayreuth Center for Molecular Biosciences - BZMB
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Profile Fields
Profile Fields > Advanced Fields
Research Institutions
Research Institutions > Research Centres
Result of work at the UBT: No
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 10 Jan 2017 10:51
Last Modified: 10 Jan 2017 10:51
URI: https://eref.uni-bayreuth.de/id/eprint/35638