Widespread occurrence of non-canonical transcription termination by human RNA polymerase III

Andrea Orioli, Chiara Pascali, Jade Quartararo, Kevin W. Diebel, Viviane Praz, David Romascano, Riccardo Percudani, Linda F. Van Dyk, Nouria Hernandez, Martin Teichmann, Giorgio Dieci

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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 T4 stretch within 50bp of 3′-flanking region. In vitro analysis of tDNAs with a distanced T4 revealed the existence of non-canonical terminators resembling degenerate T5 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.

Original languageEnglish (US)
Pages (from-to)5499-5512
Number of pages14
JournalNucleic acids research
Issue number13
StatePublished - Jul 2011

Bibliographical note

Funding Information:
Fondazione Cariparma (2010), Italian Ministry of Education, University and Research (PRIN Program), AICCRE—Regione Emilia Romagna (to G.D.); from Conseil Régional d’Aquitaine, European Regional Development Fund, Agence Nationale de la Recherche (ANR, ‘REGPOLSTRESS’) and Ligue Contre le Cancer-Comités Gironde et Dordogne (to M.T.); the National Institutes of Health (CA103632 and P30AI054907 to L.v.D.); the Burroughs Wellcome Investigator in Infectious Diseases award and a University of Colorado Technical Transfer Office award (to K.W.D. and L.v.D.). C.P. was supported by a doctoral fellowship from the ‘Università Italo-Francese/Université Franco-Italienne’. V.P., D.R. and N.H. were supported by the University of Lausanne and Swiss National Science Foundation (NSF grant 3100A0-109941 to N.H.). Funding for open access charge: Fondazione Cariparma, Parma, Italy and Conseil Régional d’Aquitaine, France.


Dive into the research topics of 'Widespread occurrence of non-canonical transcription termination by human RNA polymerase III'. Together they form a unique fingerprint.

Cite this