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Nucleic Acids Res. 2016 Apr 7;44(6):2898-908. doi: 10.1093/nar/gkw047. Epub 2016 Jan 29.

Natural antisense RNA promotes 3' end processing and maturation of MALAT1 lncRNA.

Author information

1
Department of Cell and Developmental Biology, University of Illinois Urbana, IL 61801, USA.
2
RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama 351-0198, Japan.
3
Ionis Pharmaceuticals, Carlsbad, CA, USA.
4
Center for Physics of living cells, Department of Physics, University of Illinois, Urbana, IL, USA.
5
Department of Cell and Developmental Biology, University of Illinois Urbana, IL 61801, USA kumarp@life.illinois.edu.

Abstract

The RNase P-mediated endonucleolytic cleavage plays a crucial role in the 3' end processing and cellular accumulation of MALAT1, a nuclear-retained long noncoding RNA that promotes malignancy. The regulation of this cleavage event is largely undetermined. Here we characterize a broadly expressed natural antisense transcript at the MALAT1 locus, designated as TALAM1, that positively regulates MALAT1 levels by promoting the 3' end cleavage and maturation of MALAT1 RNA. TALAM1 RNA preferentially localizes at the site of transcription, and also interacts with MALAT1 RNA. Depletion of TALAM1 leads to defects in the 3' end cleavage reaction and compromises cellular accumulation of MALAT1. Conversely, overexpression of TALAM1 facilitates the cleavage reaction in trans Interestingly, TALAM1 is also positively regulated by MALAT1 at the level of both transcription and RNA stability. Together, our data demonstrate a novel feed-forward positive regulatory loop that is established to maintain the high cellular levels of MALAT1, and also unravel the existence of sense-antisense mediated regulatory mechanism for cellular lncRNAs that display RNase P-mediated 3' end processing.

PMID:
26826711
PMCID:
PMC4824109
DOI:
10.1093/nar/gkw047
[Indexed for MEDLINE]
Free PMC Article

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