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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

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.
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Chromatin Structure Regulates pre-mRNA Processing02:41

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Riboswitches01:56

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function.

Alexander A Akerberg1,2,3, Michael Trembley1,3, Vincent Butty4,5

  • 1Division of Basic and Translational Cardiovascular Research, Department of Cardiology, Boston Children's Hospital, Boston' MA (A.A.A., M.T., X.L., W.T.P., C.E.B., C.G.B.).

Circulation Research
|November 11, 2022
PubMed
Summary

RNA-binding protein with multiple splicing (variants) 2 (RBPMS2) is crucial for heart function. Loss of RBPMS2 causes cardiac dysfunction and altered splicing in zebrafish and human cells, highlighting its conserved role in cardiovascular health.

Keywords:
RNA-binding proteinsalternative splicinghuman induced pluripotent stem cellsmyocytes, cardiaczebrafish

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Area of Science:

  • Cardiovascular Biology
  • Molecular Genetics
  • Developmental Biology

Background:

  • RNA-binding proteins (RBPs) are essential for post-transcriptional gene regulation.
  • Several RBPs are linked to cardiac development and inherited heart conditions.
  • Identifying novel cardiac RBPs is vital for cardiovascular research.

Purpose of the Study:

  • To identify novel genes, including RBPs, crucial for heart development using zebrafish.
  • To investigate the function of the myocardial-enriched gene RNA-binding protein with multiple splicing (variants) 2 (RBPMS2) in cardiac physiology.

Main Methods:

  • Differential gene expression screening in zebrafish embryos to identify genes in nkx2.5-positive cardiomyocytes.
  • Generation and characterization of rbpms2 knockout zebrafish.
  • Analysis of human cardiomyocytes derived from RBPMS2-deficient induced pluripotent stem cells.

Main Results:

  • Identified 1848 enriched genes in cardiomyocytes, including conserved RBPMS2 ohnologs (rbpms2a, rbpms2b).
  • Rbpms2 deficiency in zebrafish and human cardiomyocytes led to cardiac dysfunction, myofibril disarray, and altered calcium handling.
  • Uncovered a conserved network of 29 gene pairs regulated by RBPMS2 for alternative splicing, including RBFOX2, SLC8A1, and MYBPC3.

Conclusions:

  • RNA-binding protein with multiple splicing (variants) 2 (RBPMS2) is a conserved regulator in both zebrafish and human cardiomyocytes.
  • RBPMS2 plays a critical role in alternative splicing, myofibrillar organization, and calcium handling within the heart.