NEMF polymerizes alanine residues onto the C-terminus of the nascent peptide ("CAT tailing")

Stable Identifier
R-HSA-9948458
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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NEMF polymerizes alanine residues onto the C-terminus of the nascent peptide (
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NEMF transfers alanine residues from aminoacyl tRNAs to the C-terminus of the nascent peptide, a process termed Carboxy-terminal Alanine and Threonine tailing (CAT-tailing) (Udagawa et al. 2021, Thrun et al. 2021, inferred from the yeast homolog RQC2 in Shen et al. 2015, Kostova et al. 2017, Osuna et al. 2017). In yeast, RQC2 polymerizes a mix of alanine and threonine residues (Shen et al. 2015, Kostova et al. 2017, Osuna et al. 2017). Structures of CAT-tailing intermediates in yeast indicate that RQC2 positions an aminoacyl-tRNA in the A site of the 60S subunit and eIF5A enables peptidyl transfer (Shen et al. 2015, Tesina et al. 2023). The alanine C-terminal tails are believed to push the nascent peptide through the exit tunnel to expose lysine residues for ubiquitination by LTN1, however the alanine tails can also cause aggregation of nascent peptides (inferred from yeast homologs in Yonashiro et al. 2016). In yeast, CAT-tailing does not appear to be required for subsequent ubiquitination by LTN1 (Shen et al. 2015), but does increase the efficiency of ubiquitination in vitro (Osuna et al. 2017). Mutations that affect NEMF activity cause motor neurodegeneration in mice (Martin et al. 2020).
Literature References
PubMed ID Title Journal Year
33909987 Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing

Thrun, A, Garzia, A, Kigoshi-Tansho, Y, Patil, PR, Umbaugh, CS, Dallinger, T, Liu, J, Kreger, S, Patrizi, A, Cox, GA, Tuschl, T, Joazeiro, CAP

Mol Cell 2021
33406423 Failure to Degrade CAT-Tailed Proteins Disrupts Neuronal Morphogenesis and Cell Survival

Udagawa, T, Seki, M, Okuyama, T, Adachi, S, Natsume, T, Noguchi, T, Matsuzawa, A, Inada, T

Cell Rep 2021
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Authored
May, B  (2025-05-20)
Reviewed
Bennett, EJ  (2025-08-09)
Ford, PW  (2025-08-09)
Jafarnejad, SM  (2025-11-07)
McGirr, T  (2025-11-07)
Created
May, B  (2025-05-21)
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