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Regulation of microRNA Expression by AUF1 Through Dicer
Author(s) -
Johnson Jessica Michelle,
Tominaga Kumiko,
Gorospe Myriam,
Abdelmohsen Kotb
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.733.1
Subject(s) - dicer , drosha , microrna , ribonuclease iii , biology , microbiology and biotechnology , messenger rna , downregulation and upregulation , rna binding protein , rna interference , rna , genetics , gene
MicroRNA (miRNA) biogenesis is a tightly regulated process that involves several enzymes, including Drosha and Dicer. Although Dicer is required for the processing of all precursor microRNAs into mature microRNAs, the regulation of Dicer expression is virtually unknown. It was hypothesized that the RNA‐binding protein (RBP) AUF1 is capable of binding Dicer mRNA, causing mRNA destabilization and thereby lowering Dicer protein levels. Using immunoprecipitation of AUF1 ribonucleoprotein complexes and biotin pulldown‐in vitro binding assays, AUF1 downregulation increased Dicer mRNA stability and elevated Dicer protein levels. Conversely, AUF1 overexpression lowered Dicer mRNA and protein levels. As result of these changes in Dicer abundance, microRNA levels were also affected, with AUF1 overexpression decreasing microRNA abundance. In summary, AUF1 negatively regulates microRNA levels by lowering Dicer mRNA biosynthesis. These findings implicate microRNAs function as important regulators of gene expression and play a role in multiple cellular processes. MicroRNA expression or function is significantly altered in many disease states, including cancer, inflammatory diseases, metabolic diseases, and fibrosis.