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Related Concept Videos

RNA Splicing01:32

RNA Splicing

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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 Splicing02:18

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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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RBPMS and RBPMS2 Cooperate to Safeguard Cardiac Splicing.

Tongbin Wu, Zeyu Chen, Zengming Zhang

    Biorxiv : the Preprint Server for Biology
    |November 22, 2024
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    RNA Binding Protein with Multiple Splicing (RBPMS) and RBPMS2 proteins cooperate to regulate cardiac splicing, which is essential for heart development. Their combined action ensures proper sarcomere assembly and embryonic survival, highlighting the importance of splicing factor collaboration in cardiac health.

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    Area of Science:

    • Cardiovascular Biology
    • Molecular Biology
    • Genetics

    Background:

    • Mutations in cardiac splicing factors (SFs) are linked to cardiomyopathy and congenital heart disease.
    • Cardiac SFs are known to cooperatively regulate essential cardiac genes, but the functional significance of this collaboration is unclear.
    • RNA Binding Protein with Multiple Splicing (RBPMS) and RBPMS2 are SFs involved in heart development with similar in vitro splicing activities, but their in vivo cooperation is unknown.

    Purpose of the Study:

    • To investigate the in vivo cooperation between RBPMS and RBPMS2 in cardiac development.
    • To determine the distinct and overlapping roles of RBPMS and RBPMS2 in cardiomyocyte (CM) splicing and cardiac function.
    • To elucidate the mechanisms by which RBPMS and RBPMS2 regulate cardiac gene splicing.

    Main Methods:

    • Generation and analysis of cardiomyocyte-specific Rbpms and Rbpms2 single and double knockout (KO) mice.
    • RNA sequencing to assess gene expression and splicing changes in KO mice.
    • In silico analyses to dissect the mechanisms of RBPMS and RBPMS2 function.

    Main Results:

    • RBPMS and RBPMS2 double KO mice exhibit embryonic lethality before E13.5 and severe sarcomere disarray.
    • Single KO mice survive to adulthood with normal sarcomere assembly but display distinct cardiac phenotypes.
    • Defective sarcomere assembly in double KO mice is attributed to widespread mis-splicing of cardiac contraction genes, indicating overlapping roles for RBPMS and RBPMS2.
    • RBPMS and RBPMS2 collectively promote cardiac splicing programs and repress non-cardiac ones, with their function as activators or repressors dependent on binding location on pre-mRNA.

    Conclusions:

    • RBPMS and RBPMS2 collaborate to maintain the splicing of genes critical for cardiac contraction, safeguarding the cardiac splicing signature.
    • The cooperation between RBPMS and RBPMS2 is essential for sarcomere assembly and embryonic survival.
    • Understanding SF collaboration is crucial for developing therapeutic strategies targeting splicing factors in cardiac diseases.