## 3 eIF3f and mTOR in Skeletal Muscle Function  
The initiation of eukaryotic mRNA translation needs the cooperation of 12 eukaryotic initiation factors called \"eIFs\" forming numerous complexes. These complexes promote mRNA attachment to the ribosomal 40S subunit, mRNA scanning, start codon selection, and accommodation of initiator tRNA at the P site of the 40S subunit [146]. The mRNA eukaryotic translation initiation factor complex eIF3 is a large complex of about 800 kDa composed of 13 subunits that is essential for protein synthesis [147; 148]. eIF3 has a role at different steps of mRNA translation, including (i) the assembly of the ternary complex eIF2-GTP-Met-tRNA and its recruitment to the 40S ribosomal subunit to form the preinitiation complex 43S PIC and (ii) the mRNA recruitment to the 43S PIC and scanning for AUG codon recognition [146; 149; 150]. In mammals, an important regulator of mTORC1 activity and muscle hypertrophy is one of these subunits, the initiation factor eIF3f [40; 151] (Figure 3). eIF3f is a member of the Mov34 family with a conserved Myrr1/Pad1/N-terminal (MPN) domain. eIF3f possesses a TOS (TOR signaling) motif (FETML, amino acids 323-327) allowing eIF3f to serve as a scaffold protein to connect mTORC1 with its translational target S6K1 [151; 152]. Thus, upon mitogen/growth factor/amino acid stimulation, mTOR phosphorylates its downstream effectors to initiate mRNA translation to proteins [153]. When activated, S6K1 releases from eIF3f and phosphorylates several substrates involved in translation, such as the ribosomal protein S6, the eukaryotic elongation factor 2 (eEF2) kinase (eEF2k), and the eukaryotic translation initiation factor 4B (eIF4B) [151; 154; 155]. Of note, PDK1 catalyzes S6K1 activity through phosphorylation on residue Thr-229 for full activation [156]. In addition to its role in mRNA translation, S6K1 was also shown to regulate the transcriptional program of ribosome biogenesis [157]. S6K1-dependent regulation of this transcriptional program includes the control of nucleolar protein 56 (Nop56), nucleolar protein 14 (Nop14), GAR1 ribonucleoprotein (\"GAR\" for glycine/arginine-rich), rRNA processing 9 (Rrp9), rRNA processing 15 (Rrp15), rRNA processing 12 (Rrp12), and periodic tryptophan protein 2 (Pwpp2) nucleolar proteins [157]. S6K1 also controls Pol I through the phosphorylation of UBF enhancing rRNA synthesis (Figure 2) [158]. Furthermore, mTOR-mediated phosphorylation of 4E-BP1 (eukaryotic translation initiation factor 4E-binding protein 1) promotes its dissociation from the eukaryotic translation initiation factor 4E (eIF4E) favoring the assembly of the PIC and the recruitment of the eukaryotic translation initiation factor 4G (eIF4G) at the 5' end of mRNAs [159]. Thus, eIF3f acts as a scaffold protein to support the initiation of cap-dependent translation in mammals. However, eIF3f possesses an ambivalent function according to the cell type. Indeed, eIF3f negatively regulates cell growth by inhibiting both cap-dependent and cap-independent translation and by increasing rRNA degradation in cancer cells [160; 161]. In this model, rRNA degradation is carried out by direct interaction between eIF3f and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a RNA-binding protein required for maintaining rRNA stability [161]. eIF3f interaction with hnRNP promotes hnRNP dissociation from rRNA leading to rRNA degradation [161]. eIF3f also reduces tumor growth by interacting with the secretory heterodimeric glycoprotein clusterin and interrupting its anti-apoptotic property [162]. Interestingly, eIF3f interacts with the N-terminal region of the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV) and avian coronavirus infectious bronchitis virus (IBV) [163], opening windows for possible research on treatment of coronavirus-diseases (COVIDs). As cardiac abnormality and musculoskeletal dysfunction have been reported in COVID-19 [164; 165], this research area is currently of interest.