3’ end processing of a long nuclear-retained non-coding RNA yields a tRNA-like cytoplasmic RNA
By J. Wilusz, Susan M. Freier, David L. Spector. Cell, 2008
692 citations recorded by the source corpus.
MALAT1 is a long non-coding RNA whose expression level was originally identified as a predictor of metastasis of non-small cell lung tumors and was subsequently shown to be over-expressed in many human cancers. Here, we have identified a highly conserved tRNA-like small RNA of 61 nucleotides that originates from the MALAT1 locus and is broadly expressed in human tissues. In contrast to the long MALAT1 transcript that localizes to nuclear speckles, the small RNA exclusively localizes to the cytoplasm. We show that RNase P cleaves downstream of a genomically encoded poly(A)-rich tract to simultaneously generate the 3’ end of the abundant MALAT1 transcript and the 5’ end of the small RNA. Our findings reveal a novel 3’ end processing mechanism by which a single locus can yield both a stable nuclear retained non-coding RNA with a short poly(A) tail-like moiety and a small tRNA-like cytoplasmic RNA.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7e7507619cb2dc8a3897d085f44be2403045a02f
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In Molecular Biology
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Citations in the corpus
- The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation (2010, background): “In the present study we have examined the role of an abundant, long (>6.5 kb) mammalian nrRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1; also referred to as Neat2) in the regulation of gene expression (Hutchinson et al., 2007; Wilusz et al., 2008).”
- The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression (2012, background): “This is supported by various examples of lncRNAs that appear to operate in the cytoplasm, including MALAT1 (Wilusz et al. 2008), NRON (Willingham et al. 2005), GAS5 (Kino et al. 2010), or Thy-ncR1 (Aoki et al. 2010).”
- LncRNA: a link between RNA and cancer. (2014, background): “8 ncRNA[30], though the detailed biological function remains unclear.”
- Human tRNA-derived small RNAs in the global regulation of RNA silencing. (2010, methodology): “RNaseZ has also been recently reported to act on the nascent long noncoding human MALAT1 precursor RNA (Wilusz et al. 2008), thereby generating the mature 39 end of MALAT1 RNA and liberating a downstream cytoplasmic tRNA-like small RNA.”