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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.