title: Widespread occurrence of non-canonical transcription termination by human RNA polymerase III.
abstract: Human RNA polymerase (Pol) III-transcribed genes are thought to share a simple termination signal constituted by four or more consecutive thymidine residues in the coding DNA strand, just downstream of the RNA 3'-end sequence. We found that a large set of human tRNA genes (tDNAs) do not display any T(≥4) stretch within 50 bp of 3'-flanking region. In vitro analysis of tDNAs with a distanced T(≥4) revealed the existence of non-canonical terminators resembling degenerate T(≥5) elements, which ensure significant termination but at the same time allow for the production of Pol III read-through pre-tRNAs with unusually long 3' trailers. A panel of such non-canonical signals was found to direct transcription termination of unusual Pol III-synthesized viral pre-miRNA transcripts in gammaherpesvirus 68-infected cells. Genome-wide location analysis revealed that human Pol III tends to trespass into the 3'-flanking regions of tDNAs, as expected from extensive terminator read-through. The widespread occurrence of partial termination suggests that the Pol III primary transcriptome in mammals is unexpectedly enriched in 3'-trailer sequences with the potential to contribute novel functional ncRNAs.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Parma, Viale G.P. Usberti 23/A, 43100 Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Orioli
authors.forename: Chiara
authors.initials: C
authors.lastname: Pascali
authors.forename: Jade
authors.initials: J
authors.lastname: Quartararo
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Diebel
authors.forename: Viviane
authors.initials: V
authors.lastname: Praz
authors.forename: David
authors.initials: D
authors.lastname: Romascano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Percudani
authors.forename: Linda F
authors.initials: LF
authors.lastname: van Dyk
authors.forename: Nouria
authors.initials: N
authors.lastname: Hernandez
authors.forename: Martin
authors.initials: M
authors.lastname: Teichmann
authors.forename: Giorgio
authors.initials: G
authors.lastname: Dieci
mesh_terms: D024509:3' Flanking Region; D000818:Animals; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D012320:RNA Polymerase III / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics; D017422:Sequence Analysis, DNA; D013728:Terminator Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D012343:RNA, Transfer; D012320:RNA Polymerase III