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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Alternative exon splicing controls a translational switch from activator to repressor isoforms of transcription

W H Walker1, C Girardet, J F Habener

  • 1Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.

The Journal of Biological Chemistry
|August 16, 1996
PubMed

Insights

A novel RNA splicing event in male germ cells creates inhibitor CREB (I-CREB) isoforms. These I-CREBs regulate gene expression by blocking activator CREB binding, impacting spermatogenesis.

Area of Science:

  • Molecular Biology
  • Reproductive Biology
  • Cell Signaling

Background:

  • The cAMP/protein kinase A pathway regulates gene expression via the cAMP-responsive transcription factor CREB.
  • Spermatogenesis involves complex gene regulation crucial for male fertility.

Purpose of the Study:

  • To investigate a unique alternative RNA splicing event in CREB mRNA during male germ cell development.
  • To characterize the function and regulatory role of novel inhibitor CREB isoforms (I-CREBs) in spermatogenesis.

Main Methods:

  • Analysis of alternative RNA splicing in testicular germ cells.
  • Identification and characterization of I-CREB isoforms.
  • Investigation of I-CREB interaction with activator CREB and cAMP-responsive elements.
  • Correlation of I-CREB expression with CREB regulation during spermatogenesis.

Main Results:

  • A novel alternative splicing event produces I-CREBs from CREB mRNA in pachytene spermatocytes.
  • I-CREBs inhibit activator CREB binding to cAMP response elements, down-regulating cAMP-activated gene expression.
  • Developmental stage-specific expression of I-CREBs correlates with CREB regulation in seminiferous tubules.

Conclusions:

  • Alternative splicing generates I-CREBs, which act as negative regulators of cAMP-mediated gene expression in germ cells.
  • I-CREBs play a critical role in the cyclical regulation of gene expression during spermatogenesis.

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