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.
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http://dx.doi.org/10.1016/j.jmb.2010.07.051 | DOI Listing |
Ann Transl Med
January 2021
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Heart disease is one of the leading causes of morbidity and mortality globally. To reduce morbidity and mortality among patients with heart disease, it is important to identify drug targets and biomarkers for more effective diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) are characterized as a group of endogenous, small non-coding RNAs, which function by directly inhibiting target genes.
View Article and Find Full Text PDFFront Cell Dev Biol
June 2020
Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
The miR-15/107 group of microRNAs (miRNAs) encloses 10 annotated human members and is defined based on the presence of the sequence AGCAGC near the mature miRNAs' 5' end. Members of the miR-15/107 group expressed in humans are highly evolutionarily conserved, and seven of these miRNAs are widespread in vertebrate species. Contrary to the majority of miRNAs, which recognize complementary sequences on the 3'UTR region, some members of the miR-15/107 group are peculiarly characterized by the ability to target the coding sequence (CDS) of their target mRNAs, inhibiting translation without strongly affecting their mRNA levels.
View Article and Find Full Text PDFBMC Med Genet
May 2019
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.
Background: The highly conservative miR-15/107 family (also named as miR-15/107 gene group) including ten miRNA members is currently recognized strongly implicated in multiple human disorders. Some studies focus on the entire family rather than individual miRNA for a bigger picture, while there is also certain signature dysregulation for some of the individual miRNA implicated even in the same disorder.
Methods: Faced with the exponential growth of experimental evidence, our study tries to analyze their function and target interactions using various bioinformatics tools.
Mol Neurobiol
August 2017
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Via Viotti 3/5, 20133, Milan, Italy.
Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) encodes p35, the main activatory subunit of cyclin-dependent kinase 5 (CDK5). The p35/CDK5 active complex plays a fundamental role in brain development and functioning, but its deregulated activity has also been implicated in various neurodegenerative disorders, including Alzheimer's disease (AD). CDK5R1 displays a large and highly evolutionarily conserved 3'-untranslated region (3'-UTR), a fact that has suggested a role for this region in the post-transcriptional control of CDK5R1 expression.
View Article and Find Full Text PDFFront Genet
August 2015
Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia PA, USA.
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by degrading their RNA targets or by repressing the translation of messenger RNAs (mRNAs). Initially thought to primarily target the 3' untranslated region (3'UTR) of mRNAs, miRNAs have since been shown to also target the 5'UTR and coding sequence (CDS). In this work, we focus on the post-transcriptional regulation of the BRCA1 gene, a major tumor suppressor and regulator of double-stranded break DNA repair and show that its mRNA is targeted by many members of the miR-15/107 group at a site located within the CDS.
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