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

Abstract

MALAT1 is a long noncoding RNA known to be misregulated in many human cancers. We have identified a highly conserved small RNA of 61 nucleotides originating from the MALAT1 locus that is broadly expressed in human tissues. Although the long MALAT1 transcript localizes to nuclear speckles, the small RNA is found exclusively in the cytoplasm. RNase P cleaves the nascent MALAT1 transcript downstream of a genomically encoded poly(A)-rich tract to simultaneously generate the 3' end of the mature MALAT1 transcript and the 5' end of the small RNA. Enzymes involved in tRNA biogenesis then further process the small RNA, consistent with its adoption of a tRNA-like structure. Our findings reveal a 3' end processing mechanism by which a single gene locus can yield both a stable nuclear-retained noncoding RNA with a short poly(A) tail-like moiety and a small tRNA-like cytoplasmic RNA.