TY - JOUR
T1 - HuR counteracts miR-330 to promote STAT3 translation during inflammation-induced muscle wasting
AU - Mubaid, Souad
AU - Ma, Jennifer F.
AU - Omer, Amr
AU - Ashour, Kholoud
AU - Lian, Xian J.
AU - Sanchez, Brenda J.
AU - Robinson, Samantha
AU - Cammas, Anne
AU - Dormoy-Raclet, Virginie
AU - Marco, Sergio Di
AU - Chittur, Sridar V.
AU - Tenenbaum, Scott A.
AU - Gallouzi, Imed Eddine
N1 - Generated from Scopus record by KAUST IRTS on 2022-09-13
PY - 2019/8/27
Y1 - 2019/8/27
N2 - Debilitating cancer-induced muscle wasting, a syndrome known as cachexia, is lethal. Here we report a posttranscriptional pathway involving the RNA-binding protein HuR as a key player in the onset of this syndrome. Under these conditions, HuR switches its function from a promoter of muscle fiber formation to become an inducer of muscle loss. HuR binds to the STAT3 (signal transducer and activator of transcription 3) mRNA, which encodes one of the main effectors of this condition, promoting its expression both in vitro and in vivo. While HuR does not affect the stability and the cellular movement of this transcript, HuR promotes the translation of the STAT3 mRNA by preventing miR-330 (microRNA 330)–mediated translation inhibition. To achieve this effect, HuR directly binds to a U-rich element in the STAT3 mRNA-3′untranslated region (UTR) located within the vicinity of the miR-330 seed element. Even though the binding sites of HuR and miR-330 do not overlap, the recruitment of either one of them to the STAT3-3′UTR negatively impacts the binding and the function of the other factor. Therefore, together, our data establish the competitive interplay between HuR and miR-330 as a mechanism via which muscle fibers modulate, in part, STAT3 expression to determine their fate in response to promoters of muscle wasting.
AB - Debilitating cancer-induced muscle wasting, a syndrome known as cachexia, is lethal. Here we report a posttranscriptional pathway involving the RNA-binding protein HuR as a key player in the onset of this syndrome. Under these conditions, HuR switches its function from a promoter of muscle fiber formation to become an inducer of muscle loss. HuR binds to the STAT3 (signal transducer and activator of transcription 3) mRNA, which encodes one of the main effectors of this condition, promoting its expression both in vitro and in vivo. While HuR does not affect the stability and the cellular movement of this transcript, HuR promotes the translation of the STAT3 mRNA by preventing miR-330 (microRNA 330)–mediated translation inhibition. To achieve this effect, HuR directly binds to a U-rich element in the STAT3 mRNA-3′untranslated region (UTR) located within the vicinity of the miR-330 seed element. Even though the binding sites of HuR and miR-330 do not overlap, the recruitment of either one of them to the STAT3-3′UTR negatively impacts the binding and the function of the other factor. Therefore, together, our data establish the competitive interplay between HuR and miR-330 as a mechanism via which muscle fibers modulate, in part, STAT3 expression to determine their fate in response to promoters of muscle wasting.
UR - https://pnas.org/doi/full/10.1073/pnas.1905172116
UR - http://www.scopus.com/inward/record.url?scp=85071402381&partnerID=8YFLogxK
U2 - 10.1073/pnas.1905172116
DO - 10.1073/pnas.1905172116
M3 - Article
SN - 1091-6490
VL - 116
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 35
ER -
