RNA Ligation Procedes U6 snRNA/LINE1 Retrotransposition

Long INterspersed Element-1 (L1) amplifies via retrotransposition. Active L1s encode two proteins (ORF1p and ORF2p) that bind their encoding transcript to promote retrotransposition in cis. ORF1p and/or ORF2p also can promote the retrotransposition of Small INterspersed Element RNAs, non-coding RNAs, and messenger RNAs in trans. A class of L1-mediated retrotransposition events consist of a copy of U6 small nuclear RNA conjoined to a variably 5'-truncated L1, but how U6/L1 chimeras are formed requires elucidation. Here, we report that: U6/L1 chimeric RNAs are present in human cell lines; the RNA 2',3'-cyclic phosphate ligase protein can ligate U6 RNAs ending in a 2',3'-cyclic phosphate to L1 RNAs containing a 5'-OH group in vitro; and retrotransposition of the ligated RNAs leads to U6/L1 pseudogene formation. Thus, we have uncovered a mechanism for U6/L1 chimera formation and suggest that U6 snRNA and RtcB have biological roles in addition to their essential functions in mRNA and tRNA splicing, respectively.