9qiw
From Proteopedia
Human pre-60S - State 3
Structural highlights
FunctionIF6_HUMAN Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm (PubMed:10085284, PubMed:14654845, PubMed:21536732, PubMed:32669547). Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity).[HAMAP-Rule:MF_03132][1] [2] [3] [4] [5] Publication Abstract from PubMedThe assembly of ribosomal subunits, primarily occurring in the nucleolar and nuclear compartments, is a highly complex process crucial for cellular function. This study reveals the conservation of ribosome biogenesis between yeast and humans, illustrated by the structural similarities of ribosomal subunit intermediates. By using X-ray crystallography and cryo-EM, the interaction between the human AAA+ ATPase MDN1 and the 60S assembly factor NLE1 is compared with the yeast homologs Rea1 and Rsa4. The MDN1-MIDAS and NLE1-Ubl complex structure at 2.3 A resolution mirrors the highly conserved interaction patterns observed in yeast. Moreover, human pre-60S intermediates bound to the dominant negative NLE1-E85A mutant revealed at 2.8 A resolution an architecture that largely matched the equivalent yeast structures. Conformation of rRNA, assembly factors and their interaction networks are highly conserved. Additionally, novel human pre-60S intermediates with a non-rotated 5S RNP and processed ITS2/foot structure but incomplete intersubunit surface were identified to be similar to counterparts observed in yeast. These findings confirm that the MDN1-NLE1-driven transition phase of the 60S assembly is essentially identical, supporting the idea that ribosome biogenesis is a highly conserved process across eukaryotic cells, employing an evolutionary preservation of ribosomal assembly mechanisms. Highly conserved ribosome biogenesis pathways between human and yeast revealed by the MDN1-NLE1 interaction and NLE1 containing pre-60S subunits.,Fiorentino F, Thoms M, Wild K, Denk T, Cheng J, Zeman J, Sinning I, Hurt E, Beckmann R Nucleic Acids Res. 2025 Apr 10;53(7):gkaf255. doi: 10.1093/nar/gkaf255. PMID:40207627[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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