TY - JOUR
T1 - Long Noncoding RNA lncRNA-3 Recruits PRC2 for MyoD1 Silencing to Suppress Muscle Regeneration During Aging
AU - Zhang, Zong Kang
AU - Guan, Daogang
AU - Xu, Jintao
AU - Li, Xiaofang
AU - Zhang, Ning
AU - Yao, Shanshan
AU - Zhang, Ge
AU - Zhang, Bao Ting
N1 - Funding Information:
This research was funded by the Natural Science Foundation Council of China (82372359), Hong Kong General Research Fund (14103420, 14103121), Hong Kong Pneumoconiosis Compensation Fund Board (PCFB) (2023RS06) and Direct Grant of The Chinese University of Hong Kong (4054714).
Publisher Copyright:
© 2024 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2024/11/2
Y1 - 2024/11/2
N2 - Lowered muscle regenerative capacity in the elderly greatly contributes to the development of multiple diseases. The specific roles of long noncoding RNAs (lncRNAs) in muscle regenerative capacity during aging remain unknown. Here, we identify an elevated lncRNA (lncRNA-3), in association with reduced MyoD expression and suppressed muscle regenerative capacity, in the skeletal muscle of aged mice. LncRNA-3 could interact with both the MyoD1 promoter and RbAp46/48, a subunit of Polycomb repressive complex 2 (PRC2). LncRNA-3 could recruit PRC2 to the MyoD1 promoter and enhance the MyoD1 silencing, which, in turn, suppressed the muscle regenerative capacity. Muscle-specific lncRNA-3 knockdown could restore the muscle regenerative capacity in the aged mice. Exogenous RbAp46/48 binding motif (Rb-motif-2) treatment in skeletal muscle could compete for the lncRNA-3 binding, and therefore, enhance the muscle regenerative capacity in the aged mice. Taken together, lncRNA-3 requires PRC2 for MyoD1 silencing to suppress muscle regenerative capacity during aging. These findings provide a novel therapeutic target and a new strategy to elevate the muscle regenerative capacity in the aged population.
AB - Lowered muscle regenerative capacity in the elderly greatly contributes to the development of multiple diseases. The specific roles of long noncoding RNAs (lncRNAs) in muscle regenerative capacity during aging remain unknown. Here, we identify an elevated lncRNA (lncRNA-3), in association with reduced MyoD expression and suppressed muscle regenerative capacity, in the skeletal muscle of aged mice. LncRNA-3 could interact with both the MyoD1 promoter and RbAp46/48, a subunit of Polycomb repressive complex 2 (PRC2). LncRNA-3 could recruit PRC2 to the MyoD1 promoter and enhance the MyoD1 silencing, which, in turn, suppressed the muscle regenerative capacity. Muscle-specific lncRNA-3 knockdown could restore the muscle regenerative capacity in the aged mice. Exogenous RbAp46/48 binding motif (Rb-motif-2) treatment in skeletal muscle could compete for the lncRNA-3 binding, and therefore, enhance the muscle regenerative capacity in the aged mice. Taken together, lncRNA-3 requires PRC2 for MyoD1 silencing to suppress muscle regenerative capacity during aging. These findings provide a novel therapeutic target and a new strategy to elevate the muscle regenerative capacity in the aged population.
KW - long noncoding RNA
KW - muscle regeneration
KW - MyoD1
KW - polycomb repressive complex 2
KW - RbAp46/48
UR - http://www.scopus.com/inward/record.url?scp=85210249477&partnerID=8YFLogxK
U2 - 10.3390/ijms252212478
DO - 10.3390/ijms252212478
M3 - Journal article
AN - SCOPUS:85210249477
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 22
M1 - 12478
ER -
