Publication Date:
2007-02-27
Description:
Primary transcripts of certain microRNA (miRNA) genes are subject to RNA editing that converts adenosine to inosine. However, the importance of miRNA editing remains largely undetermined. Here we report that tissue-specific adenosine-to-inosine editing of miR-376 cluster transcripts leads to predominant expression of edited miR-376 isoform RNAs. One highly edited site is positioned in the middle of the 5'-proximal half "seed" region critical for the hybridization of miRNAs to targets. We provide evidence that the edited miR-376 RNA silences specifically a different set of genes. Repression of phosphoribosyl pyrophosphate synthetase 1, a target of the edited miR-376 RNA and an enzyme involved in the uric-acid synthesis pathway, contributes to tight and tissue-specific regulation of uric-acid levels, revealing a previously unknown role for RNA editing in miRNA-mediated gene silencing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953418/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953418/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawahara, Yukio -- Zinshteyn, Boris -- Sethupathy, Praveen -- Iizasa, Hisashi -- Hatzigeorgiou, Artemis G -- Nishikura, Kazuko -- P01 CA072765/CA/NCI NIH HHS/ -- P01 CA072765-050002/CA/NCI NIH HHS/ -- R01 GM040536/GM/NIGMS NIH HHS/ -- R01 GM040536-16/GM/NIGMS NIH HHS/ -- R01 HL070045/HL/NHLBI NIH HHS/ -- R01 HL070045-04/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1137-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. ykawahara@wistar.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17322061" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions
;
Adenosine/*metabolism
;
Adenosine Deaminase/genetics/metabolism
;
Animals
;
Base Sequence
;
Brain/metabolism
;
HeLa Cells
;
Humans
;
Inosine/*metabolism
;
Liver/metabolism
;
Mice
;
MicroRNAs/chemistry/genetics/*metabolism
;
Molecular Sequence Data
;
Nucleic Acid Conformation
;
Organ Specificity
;
Protein-Serine-Threonine Kinases/genetics/metabolism
;
*RNA Editing
;
*RNA Interference
;
RNA-Binding Proteins
;
Ribose-Phosphate Pyrophosphokinase/genetics/metabolism
;
Uric Acid/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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