Related Experiment Video
Updated: Jun 13, 2025
10:25
Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
4.8K
MBNL splicing factors regulate the microtranscriptome of skeletal muscles
Agnieszka Piasecka1, Michał W Szcześniak2, Michał Sekrecki1
1Laboratory of Gene Therapy, Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 6, 61-614 Poznań, Poland.
Nucleic Acids Research
|September 11, 2024
Summary
Muscleblind like splicing regulators (MBNLs) control RNA processing. In myotonic dystrophy type 1 (DM1), MBNL sequestration disrupts microRNA (miRNA) regulation in skeletal muscles, impacting disease progression.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Muscleblind like splicing regulators (MBNLs) are crucial for RNA processing, including alternative splicing and mRNA localization.
- In myotonic dystrophy type 1 (DM1), MBNLs are sequestered by toxic CUG repeat RNA, disrupting normal cellular functions and contributing to disease pathology.
- MicroRNAs (miRNAs) play vital roles in gene regulation and are implicated in various diseases, including muscular dystrophies.
Purpose of the Study:
- To investigate the role of MBNLs in regulating microtranscriptome dynamics during postnatal skeletal muscle development.
- To elucidate the mechanisms by which MBNL deficiency leads to miRNA misregulation in DM1.
- To identify specific miRNAs affected by MBNL insufficiency and their potential contribution to DM1 pathogenesis.
Main Methods:
- Analysis of miRNA expression profiles in Mbnl1-knockout mice and DM1 patient samples.
- Investigation of MBNL protein levels and their correlation with miRNA expression during muscle development.
- Examination of pri-miRNA levels and alternative splicing events in miRNA primary transcripts.
- Functional studies on specific miRNA clusters regulated by MBNLs.
Main Results:
- MBNLs are significant regulators of miRNA expression during postnatal skeletal muscle development.
- MBNL insufficiency leads to altered miRNA levels, with an adult-to-newborn shift observed in Mbnl1-knockout mice.
- MBNL deficiency affects miRNA biogenesis through modulation of pri-miRNA levels and alternative splicing of miRNA precursors.
- Specific miRNAs, including those from the miR-23b/27b/24-1 cluster, are sensitive to MBNL levels.
Conclusions:
- MBNL sequestration in DM1 contributes to altered miRNA activity, impacting skeletal muscle function.
- MBNLs act as key regulators of the microtranscriptome in skeletal muscle, particularly during postnatal development.
- Understanding MBNL-mediated miRNA regulation provides new insights into DM1 pathogenesis and potential therapeutic strategies.
Related Concept Videos
02:41Chromatin Structure Regulates pre-mRNA Processing
7.0K
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.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
01:32RNA Splicing
56.2K
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...
56.2K
02:18Alternative RNA Splicing
21.0K
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...
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...
21.0K
01:23Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
01:36What is Gene Expression?
8.5K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K