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Related Experiment Video

Updated: Jan 29, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting.

Cyriel S Olie¹, Muhammad Riaz¹, Rebecca Konietzny²

¹Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

|February 11, 2019

Summary

This summary is machine-generated.

Reduced poly(A)-binding protein nuclear 1 (PABPN1) levels contribute to age-related muscle wasting. Inhibiting SIRT1 deacetylase reversed this wasting by restoring PABPN1 levels, revealing a key regulatory loop.

Keywords:

Biological Sciences Molecular Biology Physiology

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Area of Science:

Molecular Biology
Aging Research
Muscle Physiology

Background:

Reduced poly(A)-binding protein nuclear 1 (PABPN1) levels are linked to aging-associated muscle wasting.
PABPN1 is a critical regulator of mRNA processing.

Purpose of the Study:

To investigate the molecular mechanisms underlying PABPN1-mediated muscle wasting.
To explore the relationship between PABPN1, protein homeostasis, and aging.

Main Methods:

Comparative transcriptome and proteome analysis in mouse muscles with reduced PABPN1 (shPab).
Proteasomal activity and acetylome profiling.
Sirtuin-1 (SIRT1) deacetylase activity assessment and inhibition studies.

Main Results:

Proteome showed greater variation than transcriptome in shPab muscles, with protein accumulation and reduced proteasomal activity.
Decreased protein acetylation and elevated SIRT1 deacetylase activity were observed in shPab muscles.
PABPN1 regulates SIRT1 mRNA via alternative polyadenylation; SIRT1 inhibition reversed muscle wasting.

Conclusions:

A regulatory loop involving PABPN1 and SIRT1 is crucial for preventing aging-associated muscle wasting.
Perturbation of this PABPN1-SIRT1 axis contributes significantly to sarcopenia.
Targeting SIRT1 offers a potential therapeutic strategy for muscle wasting conditions.