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.
Widespread occurrence of non-canonical transcription termination by human RNA polymerase III / A. Orioli; C. Pascali; J. Quartararo; K.W. Diebel; V. Praz; D. Romascano; R. Percudani; L.F. van Dyk; N. Hernandez; M. Teichmann; G. Dieci. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 39(2011), pp. 5499-5512. [10.1093/nar/gkr074]
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