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Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes
- Source :
- Nature communications. 1
- Publication Year :
- 2010
-
Abstract
- Processed pseudogenes are non-functional copies of normal genes that arise by a process of mRNA retrotransposition. The human genome contains thousands of pseudogenes; however, knowledge regarding their biological role is limited. Previously, we demonstrated that high mobility group A1 (HMGA1) protein regulates the insulin receptor (INSR) gene and that two diabetic patients demonstrated a marked destabilization of HMGA1 mRNA. In this paper we report that this destabilization of HMGA1 mRNA is triggered by enhanced expression of RNA from an HMGA1 pseudogene, HMGA1-p. Targeted knockdown of HMGA1-p mRNA in patient cells results in a reciprocal increase in HMGA1 mRNA stability and expression levels with a parallel correction in cell-surface INSR expression and insulin binding. These data provide evidence for a regulatory role of an expressed pseudogene in humans and establishes a novel mechanistic linkage between pseudogene HMGA1-p expression and type 2 diabetes mellitus.
- Subjects :
- medicine.medical_treatment
Pseudogene
Molecular Sequence Data
General Physics and Astronomy
Electrophoretic Mobility Shift Assay
Type 2 diabetes
Biology
Models, Biological
General Biochemistry, Genetics and Molecular Biology
Cell Line
Mice
Insulin resistance
Antigens, CD
medicine
Gene silencing
Animals
Humans
Gene Silencing
Gene
3' Untranslated Regions
Cells, Cultured
Genetics
HMGA Proteins
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Insulin
General Chemistry
medicine.disease
Blotting, Northern
Receptor, Insulin
High-mobility group
HEK293 Cells
Diabetes Mellitus, Type 2
Human genome
Insulin Resistance
Pseudogenes
HeLa Cells
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....27fcfbd36b6230b7c4d03b7692b0806e