TY - JOUR
T1 - Natural antisense RNA promotes 3′ end processing and maturation of MALAT1 lncRNA
AU - Zong, Xinying
AU - Nakagawa, Shinichi
AU - Freier, Susan M.
AU - Fei, Jingyi
AU - Ha, Taekjip
AU - Prasanth, Supriya G.
AU - Prasanth, Kannanganattu V.
N1 - Funding Information:
National Institute of Health [GM088252 to K.V.P., GM099669 to S.G.P.]; American Cancer Society [RSG-11-174-01-RMC to K.V.P.]; National Science Foundation career award [NSF1243372 to S.G.P.].
Publisher Copyright:
© 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2016/1/29
Y1 - 2016/1/29
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkw047
DO - 10.1093/nar/gkw047
M3 - Article
C2 - 26826711
AN - SCOPUS:84963813283
SN - 0305-1048
VL - 44
SP - 2898
EP - 2908
JO - Nucleic acids research
JF - Nucleic acids research
IS - 6
ER -