2n82

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solution structure of the complex of microRNA 20b pre-element with Rbfox RRM

Structural highlights

2n82 is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RFOX1_HUMAN RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis.[1]

Publication Abstract from PubMed

Rbfox proteins regulate tissue-specific splicing by targeting a conserved GCAUG sequence within pre-mRNAs. We report here that sequence-specific binding of the conserved Rbfox RRM to miRNA precursors containing the same sequence motif in their terminal loops, including miR-20b and miR-107, suppresses their nuclear processing. The structure of the complex between precursor miR-20b and Rbfox RRM shows the molecular basis for recognition, and reveals changes in the stem-loop upon protein binding. In mammalian cells, Rbfox2 downregulates mature miR-20b and miR-107 levels and increases the expression of their downstream targets PTEN and Dicer, respectively, suggesting that Rbfox2 indirectly regulates many more cellular miRNAs. Thus, some of the widespread cellular functions of Rbfox2 protein are attributable to regulation of miRNA biogenesis, and might include the mis-regulation of miR-20b and miR-107 in cancer and neurodegeneration.

Rbfox proteins regulate microRNA biogenesis by sequence-specific binding to their precursors and target downstream Dicer.,Chen Y, Zubovic L, Yang F, Godin K, Pavelitz T, Castellanos J, Macchi P, Varani G Nucleic Acids Res. 2016 Mar 21. pii: gkw177. PMID:27001519[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Ponthier JL, Schluepen C, Chen W, Lersch RA, Gee SL, Hou VC, Lo AJ, Short SA, Chasis JA, Winkelmann JC, Conboy JG. Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16. J Biol Chem. 2006 May 5;281(18):12468-74. Epub 2006 Mar 14. PMID:16537540 doi:http://dx.doi.org/10.1074/jbc.M511556200
  2. Chen Y, Zubovic L, Yang F, Godin K, Pavelitz T, Castellanos J, Macchi P, Varani G. Rbfox proteins regulate microRNA biogenesis by sequence-specific binding to their precursors and target downstream Dicer. Nucleic Acids Res. 2016 Mar 21. pii: gkw177. PMID:27001519 doi:http://dx.doi.org/10.1093/nar/gkw177

Contents


PDB ID 2n82

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