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SUMMARY:Regulation of microRNA biogenesis and function - Javier F Caceres\
 , MRC Human Genetics Unit\, Edinburgh
DTSTART:20101115T161500Z
DTEND:20101115T180000Z
UID:TALK27470@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:MicroRNAs (miRNAs) are small non-coding RNAs that negatively r
 egulate the expression of complementary mRNAs and affect a great diversity
  of biological processes. Their biogenesis involves a nuclear phase cataly
 zed by the Microprocessor (Drosha/DGCR8) followed by a cytoplasmic step ca
 rried out by Dicer to produce the mature miRNA.\n\nWe have shown that hnRN
 P A1\, a protein implicated in many aspects of RNA processing\, promotes t
 he Drosha-mediated processing of a miRNA precursor\, pri-miR-18a\, by bind
 ing to its conserved terminal loop (1\,2). By contrast\, hnRNP A1 can act 
 as a negative regulator of Let-7a in differentiated cells by antagonizing 
 the positive role of the KH-type splicing regulatory protein KSRP (3). Alt
 ogether\, these data suggest the existence of auxiliary factors for the pr
 ocessing of specific miRNAs that can have a positive or negative role in t
 he production of individual miRNAs.\n\n \n\nWe have used high-throughput s
 equencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP)
  to identify endogenous RNA targets of the microprocessor component\, DGCR
 8 in mammalian cells. As expected\, most of the miRNAs known to be express
 ed in 293T cells were identified\, as well as\, the DGCR8 mRNA\, which was
  known to be a target of the microprocessor complex. Other DGCR8 targets i
 nclude several hundred mRNAs\, non-coding RNAs\, snoRNAs and retrotranspos
 ons. Further analysis and validation of these data will provide insights i
 n the complex role of the DGCR8 in controlling the fate of different class
 es of cellular RNAs.\n\n \n\n1. Guil\,S. and Cáceres\,J.F. (2007) The mul
 tifunctional RNA-binding protein hnRNP A1 is required for processing of mi
 R-18a. Nat. Struct. Mol. Biol.\, 14\, 591-596.\n\n2. Michlewski\,G. et al.
  (2008) Mol Cell\, 32\, 383-393.\n\n3. Michlewski\,G. and Cáceres\,J.F. (
 2010) Nat. Struct. Mol. Biol.\, 17\, 1011-1018.\n\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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