Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells

• Published in: EMBO reports Vol. 11; no. 2; pp. 106 - 111
• Main Authors: Shcherbik, Natalia, Wang, Minshi, Lapik, Yevgeniya R, Srivastava, Leena, Pestov, Dimitri G
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2010; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: actinomycin D; Animals; Biological properties; Cellular biology; Codon, Nonsense - genetics; Codon, Nonsense - metabolism; Dactinomycin - pharmacology; EMBO36; Eukaryotic Cells - metabolism; exosome; Gene Expression Regulation, Enzymologic - drug effects; Humans; Mammals; Mammals - genetics; Mammals - metabolism; Metazoa; Mice; Molecular biology; NIH 3T3 Cells; non-canonical poly(A) polymerase; Polyadenylation - physiology; Protein Synthesis Inhibitors - pharmacology; Proteins; Quality control; ribosomal RNA; RNA polymerase; RNA Polymerase I - genetics; RNA Polymerase I - metabolism; RNA processing; RNA Stability - physiology; RNA, Messenger - analysis; RNA, Messenger - metabolism; Scientific Report; Transfection; actinomycin D; ribosomal RNA; RNA processing; exosome; non‐canonical poly(A) polymerase
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2009.271

Most transcripts in growing cells are ribosomal RNA precursors (pre‐rRNA). Here, we show that in mammals, aberrant pre‐rRNA transcripts generated by RNA polymerase I (Pol I) are polyadenylated and accumulate markedly after treatment with low concentrations of actinomycin D (ActD), which blocks the synthesis of full‐length rRNA. The poly(A) polymerase‐associated domain‐containing protein 5 is required for polyadenylation, whereas the exosome is partly responsible for the degradation of the short aberrant transcripts. Thus, polyadenylation functions in the quality control of Pol I transcription in metazoan cells. The impact of excessive aberrant RNAs on the degradation machinery is an unrecognized mechanism that might contribute to biological properties of ActD. Pestov and colleagues demonstrate that polyadenylation acts as a surveillance mechanism for aberrant RNA Polymerase I transcripts in mammals and find a role for the noncanonical poly(A) polymerase PAPD5 and the exosome in this process. The authors also show that polyadenylated truncated pre‐rRNA species accumulate when cells are treated with low doses of actinomycin D, thus revealing a previously unknown property of a drug commonly utilized to block rRNA synthesis.