Related Experiment Video

Updated: Dec 9, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.9K

METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth

Valentina V Ignatova1, Steffen Kaiser2, Jessica Sook Yuin Ho3,4

  • 1Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Science Advances
|September 14, 2020
PubMed

Insights

Methyltransferase-like protein 6 (METTL6) regulates hepatocellular carcinoma (HCC) cell growth by methylating transfer RNA (tRNA). METTL6 is crucial for stem cell renewal and impacts tumor cell proliferation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • RNA modifications, including methylation, are vital regulators of RNA biology.
  • These modifications are increasingly linked to various diseases, notably cancer.
  • Hepatocellular carcinoma (HCC) progression is influenced by complex molecular mechanisms.

Purpose of the Study:

  • To identify novel methyltransferases involved in hepatocellular carcinoma (HCC) cell proliferation.
  • To elucidate the specific role and mechanism of action of identified methyltransferases in cancer and stem cell biology.

Main Methods:

  • In vitro and in vivo screening of 78 potential methyltransferases.
  • Biochemical assays to characterize methyltransferase activity.
  • Genetic manipulation (gene deletion/knockout) in mouse models and cell lines.

Main Results:

  • Methyltransferase-like protein 6 (METTL6) was identified as a key regulator of HCC cell growth.
  • METTL6 was confirmed as a transfer RNA (tRNA) methyltransferase, catalyzing 3-methylcytidine formation at C32 of specific serine tRNA isoacceptors.
  • Mettl6 deletion in mouse stem cells impaired pluripotency and altered ribosome occupancy and RNA levels.
  • Mettl6 knockout in mice led to reduced energy expenditure.

Conclusions:

  • METTL6 is a critical regulator of stem cell self-renewal through its role in maintaining translation efficiency.
  • METTL6 significantly impacts hepatocellular carcinoma cell proliferation, presenting a potential therapeutic target.
  • This study reveals a novel pathway involving tRNA methylation in stem cell maintenance and cancer biology.

More Related Videos

Antibody-Free Assay for RNA Methyltransferase Activity Analysis08:31

Antibody-Free Assay for RNA Methyltransferase Activity Analysis

Published on: July 9, 2019

7.5K
An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C11:53

An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C

Published on: June 1, 2018

6.9K

Related Concept Videos

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...
7.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.1K
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.5K
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...
4.5K
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.1K