9c3h
From Proteopedia
Structure of the CNOT3-bound human 80S ribosome with tRNA-ARG in the P-site.
Structural highlights
DiseaseRL5_HUMAN Blackfan-Diamond disease. Diamond-Blackfan anemia 6 (DBA6) [MIM:612561: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] [2] FunctionRL5_HUMAN Required for rRNA maturation and formation of the 60S ribosomal subunits. This protein binds 5S RNA.[3] Publication Abstract from PubMedThe CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation. We applied selective ribosome profiling to further investigate the determinants of CCR4-NOT recruitment to ribosomes in mammalian cells. This revealed that specific arginine codons in the P-site are strong signals for ribosomal recruitment of human CNOT3, a CCR4-NOT subunit. Cryo-electron microscopy and transfer RNA (tRNA) mutagenesis demonstrated that the D-arms of select arginine tRNAs interact with CNOT3 and promote its recruitment whereas other tRNA D-arms sterically clash with CNOT3. These effects link codon content to mRNA stability. Thus, in addition to their canonical decoding function, tRNAs directly engage regulatory complexes during translation, a mechanism we term P-site tRNA-mediated mRNA decay. Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes.,Zhu X, Cruz VE, Zhang H, Erzberger JP, Mendell JT Science. 2024 Nov 22;386(6724):eadq8587. doi: 10.1126/science.adq8587. Epub 2024 , Nov 22. PMID:39571015[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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