3′ End Processing of a Long Nuclear-Retained Noncoding RNA Yields a tRNA-like Cytoplasmic RNA

Abstract

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.

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

“…Some lncRNAs may function as precursors for the generation of sRNAs (ENCODE Project Consortium et al 2007;Wilusz et al 2008). To identify sRNA-precursor lncRNAs, we compared our lncRNA transcripts to a set of sRNAs present in 2-d-old zebrafish (Methods; Cifuentes et al 2010).…”

“…Other lncRNAs may act as decoys in the sequestration of miRNAs (Poliseno et al 2010), transcription factors (Hung et al 2011), or other proteins (Tripathi et al 2010). Yet others may serve as precursors for the generation of sRNAs (Kapranov et al 2007;Wilusz et al 2008;Fejes-Toth et al 2009). …”

Long non-coding RNAs in cancer

“…Cellular MALAT1 can be posttranscriptionally processed to yield the short, highly conserved, tRNA-like molecule mascRNA and the long MALAT1 transcript, which contains a poly(A) tail-like moiety [57]. MALAT1 is expressed in normal human tissues and exhibits increased expression in cancers of the breast, prostate, colon, liver, lung and others [58].…”

A stable tRNA-like molecule is generated from the long noncoding RNA GUT15 in Arabidopsis

“…A similar mechanism has been reported for two tRNA-like molecules generated from the mammalian lncRNAs MALAT1 and Menβ . In both cases, RNase P recognizes the tRNA-like structure in a nascent RNAPII transcript and cleaves it to simultaneously generate the 3′-end of the mature nuclear-retained lncRNA and the 5′-end of the tRNA-like small RNA [31, 32]. Recently, 132 genomic loci resembling the MALAT1 3′-end processing module have been identified among several vertebrate genomes [33].…”

“…Recently, 132 genomic loci resembling the MALAT1 3′-end processing module have been identified among several vertebrate genomes [33]. Interestingly, both mascRNAs (MALAT1-associated small cytoplasmic RNAs) and the GUT15 -tRNA-like molecule are marked with a CCA [31]. Furthermore, the RNAPII-mediated transcription of conventional tRNAs has been already reported for tRNA Sec in Trypanosoma brucei [34].…”