Related Experiment Video

Updated: May 12, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
12:07

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Published on: November 22, 2014

13.9K

METTL3-dependent m6A modification of GHR mRNA regulates mitochondrial function through mitochondrial biogenesis

Changbin Zhao1, Bowen Hu1, Zhijun Wang1

  • 1State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Lingnan Guangdong Laboratory of Agriculture, College of Animal Science, South China Agricultural University, Guangzhou 510642, China; National-Local Joint Engineering Research Center for Livestock Breeding, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, China.

Poultry Science
|May 9, 2025
PubMed

Insights

N6-methyl-adenosine (m6A) modification regulates growth hormone receptor (GHR) mRNA expression, impacting muscle development. This epigenetic process inhibits mitochondrial function and biogenesis during myoblast differentiation.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Muscle Development

Background:

  • N6-methyl-adenosine (m6A) methylation is crucial for muscle development.
  • Growth hormone receptor (GHR) knockdown impairs mitochondrial function and myoblast differentiation.
  • m6A modification peaks were identified in chicken GHR mRNA.

Purpose of the Study:

  • To investigate the role of m6A modification in regulating GHR mRNA expression.
  • To determine the impact of m6A-mediated GHR regulation on mitochondrial function and biogenesis during myoblast differentiation.

Main Methods:

  • Bioinformatic prediction of m6A sites on GHR mRNA using SRAMP.
  • Experimental validation of m6A modification site (GHR-139) and its dependence on METTL3.
  • Analysis of GHR mRNA and protein expression, GH-GHR-IGFs axis signaling, mitochondrial function, and biogenesis.
  • Investigation of m6A reader proteins (hnRNPR, hnRNPA3, hnRNPM).

Main Results:

  • METTL3-dependent m6A modification at GHR-139 down-regulates GHR mRNA and protein expression.
  • This m6A modification inhibits the GH-GHR-IGFs axis signaling pathway.
  • METTL3-dependent m6A modification suppresses mitochondrial biogenesis and impairs mitochondrial function.
  • Overexpression of METTL3 alone inhibited GHR expression, mitochondrial biogenesis, and function.
  • hnRNPR, hnRNPA3, and hnRNPM were identified as potential m6A reader proteins involved in GHR regulation.

Conclusions:

  • METTL3-dependent m6A modification of GHR mRNA plays a significant role in muscle development.
  • This epigenetic regulation impairs mitochondrial function by inhibiting mitochondrial biogenesis during myoblast differentiation.
  • The findings elucidate a novel mechanism linking m6A modification, GHR signaling, and muscle energetics.
Keywords:
GHRMETTL3Mitochondrial biogenesisMitochondrial functionm(6)A

More Related Videos

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling08:34

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling

Published on: December 18, 2017

6.5K
In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

1.3K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
Master Transcription Regulators02:23

Master Transcription Regulators

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...
6.7K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.2K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.5K