Opposing regulation of the Nα-trimethylase METTL11A by its family members METTL11B and METTL13

Parker, HaleyV.; Tooley, ChristineE. Schaner

doi:10.1016/j.jbc.2023.104588

Cited by 4 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another mode of regulation is through complex formation with close MTase family members. NTMT1 is activated through the binding of its close homolog NTMT2, while METTL13 inhibits NTMT2 activity ( 112 ). This is an interesting example of MTases being regulated oppositely by different family members.…”

Section: Regulation Of Ntmts Functionmentioning

confidence: 99%

“…This is an interesting example of MTases being regulated oppositely by different family members. Moreover, catalytic activity is not a requirement for these regulatory effects, demonstrating new, noncatalytic functions for NTMT1 and METTL13 ( 112 ). When all three are present, the regulatory effects of METTL13 override those of NTMT2.…”

Section: Regulation Of Ntmts Functionmentioning

confidence: 99%

See 1 more Smart Citation

Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions

Chen

Huang

Hazbun

2023

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Regulation Of Ntmts Functionmentioning

confidence: 99%

Section: Regulation Of Ntmts Functionmentioning

confidence: 99%

Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions

Chen

Huang

Hazbun

2023

Journal of Biological Chemistry

View full text Add to dashboard Cite

Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation

Hobble,

Schaner Tooley

2024

Epigenetics & Chromatin

View full text Add to dashboard Cite

Protein and nucleic acid methylation are important biochemical modifications. In addition to their well-established roles in gene regulation, they also regulate cell signaling, metabolism, and translation. Despite this high biological relevance, little is known about the general regulation of methyltransferase function. Methyltransferases are divided into superfamilies based on structural similarities and further classified into smaller families based on sequence/domain/target similarity. While members within superfamilies differ in substrate specificity, their structurally similar active sites indicate a potential for shared modes of regulation. Growing evidence from one superfamily suggests a common regulatory mode may be through heterooligomerization with other family members. Here, we describe examples of methyltransferase regulation through intrafamily heterooligomerization and discuss how this can be exploited for therapeutic use.

show abstract

Three's a crowd – why did three N-terminal methyltransferases evolve for one job?

Conner

Tooley

2023

Journal of Cell Science

View full text Add to dashboard Cite

N-terminal methylation of the α-amine group (Nα-methylation) is a post-translational modification (PTM) that was discovered over 40 years ago. Although it is not the most abundant of the Nα-PTMs, there are more than 300 predicted substrates of the three known mammalian Nα-methyltransferases, METTL11A and METTL11B (also known as NTMT1 and NTMT2, respectively) and METTL13. Of these ∼300 targets, the bulk are acted upon by METTL11A. Only one substrate is known to be Nα-methylated by METTL13, and METTL11B has no proven in vivo targets or predicted targets that are not also methylated by METTL11A. Given that METTL11A could clearly handle the entire substrate burden of Nα-methylation, it is unclear why three distinct Nα-methyltransferases have evolved. However, recent evidence suggests that many methyltransferases perform important biological functions outside of their catalytic activity, and the Nα-methyltransferases might be part of this emerging group. Here, we describe the distinct expression, localization and physiological roles of each Nα-methyltransferase, and compare these characteristics to other methyltransferases with non-catalytic functions, as well as to methyltransferases with both catalytic and non-catalytic functions, to give a better understanding of the global roles of these proteins. Based on these comparisons, we hypothesize that these three enzymes do not just have one common function but are actually performing three unique jobs in the cell.

show abstract

Opposing regulation of the Nα-trimethylase METTL11A by its family members METTL11B and METTL13

Cited by 4 publications

References 54 publications

Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions

Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions

Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation

Three's a crowd – why did three N-terminal methyltransferases evolve for one job?

Contact Info

Product

Resources

About