Both endonucleolytic and exonucleolytic cleavage mediate ITS1 removal during human ribosomal RNA processing |
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| Authors: | Katherine E Sloan Sandy Mattijssen Simon Lebaron David Tollervey Ger JM Pruijn Nicholas J Watkins |
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| Institution: | 1.Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, England, UK;2.Nijmegen Center for Molecular Life Sciences, and 3.Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen NL-6500 HB, Netherlands;4.Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK |
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| Abstract: | Human ribosome production is up-regulated during tumorogenesis and is defective in many genetic diseases (ribosomopathies). We have undertaken a detailed analysis of human precursor ribosomal RNA (pre-rRNA) processing because surprisingly little is known about this important pathway. Processing in internal transcribed spacer 1 (ITS1) is a key step that separates the rRNA components of the large and small ribosomal subunits. We report that this was initiated by endonuclease cleavage, which required large subunit biogenesis factors. This was followed by 3′ to 5′ exonucleolytic processing by RRP6 and the exosome, an enzyme complex not previously linked to ITS1 removal. In contrast, RNA interference–mediated knockdown of the endoribonuclease MRP did not result in a clear defect in ITS1 processing. Despite the apparently high evolutionary conservation of the pre-rRNA processing pathway and ribosome synthesis factors, each of these features of human ITS1 processing is distinct from those in budding yeast. These results also provide significant insight into the links between ribosomopathies and ribosome production in human cells. |
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