METTLing in Stem Cell and Cancer Biology

The methyltransferase-like (METTL) family is a diverse group of methyltransferases that can methylate nucleotides, proteins, and small molecules. Despite this diverse array of substrates, they all share a characteristic seven-beta-strand catalytic domain, and recent evidence suggests many also share...

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Published inStem cell reviews and reports Vol. 19; no. 1; pp. 76 - 91
Main Authors Tooley, John G., Catlin, James P., Tooley, Christine E. Schaner
Format Journal Article
LanguageEnglish
Published New York Springer US 01.01.2023
Springer Nature B.V
Subjects
Animal models
Animals
Biology
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Cell Biology
Cell differentiation
Cell Differentiation - genetics
Cell self-renewal
Embryogenesis
Embryonic Stem Cells
Hematopoietic stem cells
Life Sciences
Mesenchyme
Methyltransferases - genetics
Methyltransferases - metabolism
Mice
N6-methyladenosine
Neoplasms - genetics
Neoplasms - metabolism
Neural stem cells
Nucleotides
Pluripotency
Regenerative Medicine/Tissue Engineering
RNA - metabolism
Roles
Stem Cells
Tumorigenesis
Translation
Transcription
Stem cell
Methyltransferase
METTL
Metabolism
Cancer
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Summary:The methyltransferase-like (METTL) family is a diverse group of methyltransferases that can methylate nucleotides, proteins, and small molecules. Despite this diverse array of substrates, they all share a characteristic seven-beta-strand catalytic domain, and recent evidence suggests many also share an important role in stem cell biology. The most well characterized family members METTL3 and METTL14 dimerize to form an N 6 -methyladenosine (m 6 A) RNA methyltransferase with established roles in cancer progression. However, new mouse models indicate that METTL3/METTL14 are also important for embryonic stem cell (ESC) development and postnatal hematopoietic and neural stem cell self-renewal and differentiation. METTL1, METTL5, METTL6, METTL8, and METTL17 also have recently identified roles in ESC pluripotency and differentiation, while METTL11A/11B, METTL4, METTL7A, and METTL22 have been shown to play roles in neural, mesenchymal, bone, and hematopoietic stem cell development, respectively. Additionally, a variety of other METTL family members are translational regulators, a role that could place them as important players in the transition from stem cell quiescence to differentiation. Here we will summarize what is known about the role of METTL proteins in stem cell differentiation and highlight the connection between their growing importance in development and their established roles in oncogenesis. Graphical abstract
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Authors’ contributions JGT and CST co-wrote the majority of the manuscript. JC wrote the sections on neural stem cells. CST created the figures.
ISSN:2629-3269
2629-3277
DOI:10.1007/s12015-022-10444-7