NDLI: Gradual processing of the ITS1 from the nucleolus to the cytoplasm during synthesis of the human 18S rRNA

Content Provider	PubMed Central
Author	Preti, Milena O'donohue, Marie-françoise Montel-lehry, Nathalie Bortolin-cavaillé, Marie-line Choesmel, Valérie Gleizes, Pierre-emmanuel
Copyright Year	2013
Abstract	Defects in ribosome biogenesis trigger stress response pathways, which perturb cell proliferation and differentiation in several genetic diseases. In Diamond–Blackfan anemia (DBA), a congenital erythroblastopenia, mutations in ribosomal protein genes often interfere with the processing of the internal transcribed spacer 1 (ITS1), the mechanism of which remains elusive in human cells. Using loss-of-function experiments and extensive RNA analysis, we have defined the precise position of the endonucleolytic cleavage E in the ITS1, which generates the 18S-E intermediate, the last precursor to the 18S rRNA. Unexpectedly, this cleavage is followed by 3′–5′ exonucleolytic trimming of the 18S-E precursor during nuclear export of the pre-40S particle, which sets a new mechanism for 18S rRNA formation clearly different from that established in yeast. In addition, cleavage at site E is also followed by 5′–3′ exonucleolytic trimming of the ITS1 by exonuclease XRN2. Perturbation of this step on knockdown of the large subunit ribosomal protein RPL26, which was recently associated to DBA, reveals the putative role of a highly conserved cis-acting sequence in ITS1 processing. These data cast new light on the original mechanism of ITS1 elimination in human cells and provide a mechanistic framework to further study the interplay of DBA-linked ribosomal proteins in this process.
Related Links	http://dx.doi.org/10.1093/nar/gkt160
Ending Page	4723
Page Count	15
Starting Page	4709
File Format	PDF
ISSN	13624962
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	8
Volume Number	41
Language	English
Publisher	Oxford University Press
Publisher Date	2013-04-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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