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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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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.
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Alternative splicing impairs soluble guanylyl cyclase function in aortic aneurysm.

Emil Martin1, Eva Golunski1, Susan T Laing1

  • 1Department of Internal Medicine/Cardiology, The University of Texas Health Science Center in Houston Medical School, Houston, Texas; and.

American Journal of Physiology. Heart and Circulatory Physiology
|September 21, 2014
PubMed
Summary

Alternative splicing of soluble guanylyl cyclase (sGC) impacts vascular function. This study reveals altered sGC splice variants in aortic aneurysms, contributing to reduced sGC activity and potential therapeutic targets.

Keywords:
alternative splicingaortanitric oxidesoluble guanylyl cyclase

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Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Vascular Medicine

Background:

  • Soluble guanylyl cyclase (sGC) is crucial for vascular homeostasis and plasticity.
  • Reduced sGC function is implicated in cardiovascular diseases, but its regulation in vascular tissue is unclear.
  • Alternative splicing of sGC genes influences sGC function.

Purpose of the Study:

  • To investigate the role of alternative splicing of α1 and β1 sGC in healthy and diseased human vascular tissue.
  • To analyze sGC splice variant composition in human aortas with and without aneurysms.

Main Methods:

  • Analysis of α1 and β1 sGC splice forms in human aortic tissue samples.
  • Comparison of splice variant abundance and sGC activity between aneurysm and non-aneurysm samples.
  • Assessment of the impact of the α1-IsoB splice variant on sGC activity.

Main Results:

  • Diverse α1 and β1 sGC splice forms are expressed in the human aorta.
  • Aneurysmal aortas exhibit different splice variant profiles and reduced sGC activity compared to healthy aortas.
  • Increased expression of dysfunctional sGC splice variants and decreased expression of the protective α1-IsoB isoform were observed in aneurysmal aortas.

Conclusions:

  • Alternative splicing contributes to diminished sGC function in vascular dysfunction, particularly in aortic aneurysms.
  • The α1-IsoB splice variant supports sGC activity and its reduced expression in aneurysms is significant.
  • Understanding sGC splicing regulation may lead to novel therapeutic strategies for vascular diseases.