Dataset Information

Brain-expressed 3'UTR extensions strengthen miRNA cross-talk between ion channel/transporter encoding mRNAs.

ABSTRACT: Why protein-coding genes express transcripts with longer 3'untranslated regions (3'UTRs) in the brain rather than in other tissues remains poorly understood. Given the established role of 3'UTRs in post-transcriptional regulation of transcript abundance and their recently highlighted contributions to miRNA-mediated cross-talk between mRNAs, we hypothesized that 3'UTR lengthening enhances coordinated expression between functionally-related genes in the brain. To test this hypothesis, we annotated 3'UTRs of human brain-expressed genes and found that transcripts encoding ion channels or transporters are specifically enriched among those genes expressing their longest 3'UTR extension in this tissue. These 3'UTR extensions have high density of response elements predicted for those miRNAs that are specifically expressed in the human frontal cortex (FC). Importantly, these miRNA response elements are more frequently shared among ion channel/transporter-encoding mRNAs than expected by chance. This indicates that miRNA-mediated cross-talk accounts, at least in part, for the observed coordinated expression of ion channel/transporter genes in the adult human brain. We conclude that extension of these genes' 3'UTRs enhances the miRNA-mediated cross-talk among their transcripts which post-transcriptionally regulates their mRNAs' relative levels.

SUBMITTER: Wehrspaun CC

PROVIDER: S-EPMC3935148 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Brain-expressed 3'UTR extensions strengthen miRNA cross-talk between ion channel/transporter encoding mRNAs.

Wehrspaun Claudia C CC Ponting Chris P CP Marques Ana C AC

Frontiers in genetics 20140226

Why protein-coding genes express transcripts with longer 3'untranslated regions (3'UTRs) in the brain rather than in other tissues remains poorly understood. Given the established role of 3'UTRs in post-transcriptional regulation of transcript abundance and their recently highlighted contributions to miRNA-mediated cross-talk between mRNAs, we hypothesized that 3'UTR lengthening enhances coordinated expression between functionally-related genes in the brain. To test this hypothesis, we annotated ...[more]

PMID: 24616735

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Project description:SLC39A8 is an evolutionarily highly conserved gene that encodes the ZIP8 metal cation transporter in all vertebrates. SLC39A8 is ubiquitously expressed, including pluripotent embryonic stem cells; SLC39A8 expression occurs in every cell type examined. Uptake of ZIP8-mediated Mn2+, Zn2+, Fe2+, Se4+, and Co2+ represents endogenous functions-moving these cations into the cell. By way of mouse genetic differences, the phenotype of "subcutaneous cadmium-induced testicular necrosis" was assigned to the Cdm locus in the 1970s. This led to identification of the mouse Slc39a8 gene, its most closely related Slc39a14 gene, and creation of Slc39a8-overexpressing, Slc39a8(neo/neo) knockdown, and cell type-specific conditional knockout mouse lines; the Slc39a8(-/-) global knockout mouse is early-embryolethal. Slc39a8(neo/neo) hypomorphs die between gestational day 16.5 and postnatal day 1-exhibiting severe anemia, dysregulated hematopoiesis, hypoplastic spleen, dysorganogenesis, stunted growth, and hypomorphic limbs. Not surprisingly, genome-wide association studies subsequently revealed human SLC39A8-deficiency variants exhibiting striking pleiotropy-defects correlated with clinical disorders in virtually every organ, tissue, and cell-type: numerous developmental and congenital disorders, the immune system, cardiovascular system, kidney, lung, liver, coagulation system, central nervous system, musculoskeletal system, eye, and gastrointestinal tract. Traits with which SLC39A8-deficiency variants are currently associated include Mn2+-deficient hypoglycosylation; numerous birth defects; Leigh syndrome-like mitochondrial redox deficiency; decreased serum high-density lipoprotein-cholesterol levels; increased body mass index; greater risk of coronary artery disease, hypotension, cardiovascular death, allergy, ischemic stroke, schizophrenia, Parkinson disease, inflammatory bowel disease, Crohn disease, myopia, and adolescent idiopathic scoliosis; systemic lupus erythematosus with primary Sjögren syndrome; decreased height; and inadvertent participation in the inflammatory progression of osteoarthritis.

Dataset Information

Brain-expressed 3'UTR extensions strengthen miRNA cross-talk between ion channel/transporter encoding mRNAs.

Publications

Brain-expressed 3'UTR extensions strengthen miRNA cross-talk between ion channel/transporter encoding mRNAs.

Similar Datasets

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