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PMID: 20678503 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases.

Journal of molecular biology ·Vol. 402 ·No. 3 ·2010-09-24 ·Pages 491-509

Finnerty JR, Wang WX, Hébert SS, Wilfred BR, Mao G, Nelson PT

Abstract

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played by these miRNAs in human diseases. Membership in this group is defined based on sequence similarity near the mature miRNAs' 5' end: all include the sequence AGCAGC. Phylogeny of this group of miRNAs is incomplete; thus, a definitive taxonomic classification (e.g., designation as a "superfamily") is currently not possible. While all vertebrates studied to date express miR-15a, miR-15b, miR-16, miR-103, and miR-107, mammals alone are known to express miR-195, miR-424, miR-497, miR-503, and miR-646. Multiple different miRNAs in the miR-15/107 group are expressed at moderate to high levels in human tissues. We present data on the expression of all known miR-15/107 group members in human cerebral cortical gray matter and white matter using new miRNA profiling microarrays. There is extensive overlap in the mRNAs targeted by miR-15/107 group members. We show new data from cultured H4 cancer cells that demonstrate similarities in mRNAs targeted by miR-16 and miR-103 and also support the importance of the mature miRNAs' 5' seed region in mRNA target recognition. In conclusion, the miR-15/107 group of miRNA genes is a fascinating topic of study for evolutionary biologists, miRNA biochemists, and clinically oriented translational researchers alike.

MeSH Terms
Animals Cell Proliferation Cerebral Cortex/metabolism Evolution, Molecular Gene Expression Regulation Heart Diseases/genetics Humans MicroRNAs/physiology Neoplasms/genetics Neovascularization, Pathologic/genetics Neovascularization, Physiologic/genetics Neurodegenerative Diseases/genetics Oligonucleotide Array Sequence Analysis
Chemicals
MicroRNAs
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Finnerty John R
Division of Neuropathology, Department of Pathology, University of Kentucky Medical Center and Sanders-BrownCenter on Aging, University of Kentucky, Lexington, KY 40536, USA.
Wang Wang-Xia
Hébert Sébastien S
Wilfred Bernard R
Mao Guogen
Nelson Peter T
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Article Info
Journal
Journal of molecular biology
Abbr.
J Mol Biol
ISSN
1089-8638
DOI
10.1016/j.jmb.2010.07.051
Published
2010-09-24
Epub
2010-00-01
Pages
491-509
Language
English
Region
England
NLM ID
2985088R
PMCID
PMC2978331
Subset
IM
Grants
NINDS NIH HHS · K08 NS050110-02 · United States
NINDS NIH HHS · K08 NS050110 · United States
NINDS NIH HHS · R01 NS061933-01A1 · United States
NIA NIH HHS · R21 AG036875-01A1 · United States
NINDS NIH HHS · R01 NS061933 · United States
NIA NIH HHS · P30-AG028383 · United States
NIA NIH HHS · R21 AG036875 · United States
NIA NIH HHS · P30 AG028383 · United States
External Links
PubMed source DOI: 10.1016/j.jmb.2010.07.051 PMC Full Text View journal details
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