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Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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RNA Splicing01:32

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Investigation of Beige Fat Biology and Metabolism Using the CRISPR SunTag-p65-HSF1 Activation System
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An alternative splicing program promotes adipose tissue thermogenesis.

Santiago Vernia1, Yvonne Jk Edwards1, Myoung Sook Han1

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.

Elife
|September 17, 2016
PubMed
Summary
This summary is machine-generated.

Alternative splicing in fat cells (adipocytes) impacts obesity. NOVA proteins suppress fat tissue thermogenesis, and their deficiency improves blood sugar control.

Keywords:
JNKNOVAadipocytecell biologyhigh fat diethumanmousepre-mRNA splicingthermogenesis

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Area of Science:

  • Molecular Biology
  • Metabolism
  • Genomics

Background:

  • Alternative pre-mRNA splicing generates diverse transcripts, influencing gene expression.
  • The role of alternative splicing in metabolic regulation, particularly in obesity, remains largely unexplored.
  • Adipocyte function is critical for energy homeostasis and metabolic health.

Purpose of the Study:

  • To investigate the contribution of alternative splicing to diet-induced obesity.
  • To identify splicing factors involved in obesity-related gene expression changes in adipocytes.
  • To elucidate the role of NOVA splicing factors in adipose tissue thermogenesis and glucose metabolism.

Main Methods:

  • Quantitative analysis of gene expression at the exon level in adipocytes from diet-induced obese models.
  • Bioinformatic analysis to identify splicing factor binding sites and associated splicing programs.
  • Phenotypic analysis of mice with adipocyte-specific deficiency in NOVA splicing factors.

Main Results:

  • Obesity induces significant changes in alternative pre-mRNA splicing patterns within adipocytes.
  • A subset of obesity-associated alternative splicing is regulated by sequence-specific NOVA splicing factors.
  • NOVA deficiency in adipocytes leads to enhanced adipose tissue thermogenesis and improved glycemic control.
  • NOVA proteins mediate a splicing program that actively suppresses adipose tissue thermogenesis.

Conclusions:

  • Alternative splicing is a key regulator in the development of diet-induced obesity.
  • NOVA splicing factors play a critical role in suppressing adipose tissue thermogenesis.
  • Targeting NOVA-mediated splicing offers a novel therapeutic avenue for metabolic disorders like obesity and hyperglycemia.