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9c3h

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Structure of the CNOT3-bound human 80S ribosome with tRNA-ARG in the P-site.

Structural highlights

9c3h is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2Å
Ligands:	, , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RL5_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]

Function

RL5_HUMAN Required for rRNA maturation and formation of the 60S ribosomal subunits. This protein binds 5S RNA.^[3]

Publication Abstract from PubMed

The 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

↑ Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. PMID:19061985 doi:S0002-9297(08)00589-2
↑ Cmejla R, Cmejlova J, Handrkova H, Petrak J, Petrtylova K, Mihal V, Stary J, Cerna Z, Jabali Y, Pospisilova D. Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond-Blackfan anemia. Hum Mutat. 2009 Mar;30(3):321-7. doi: 10.1002/humu.20874. PMID:19191325 doi:10.1002/humu.20874
↑ Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. PMID:19061985 doi:S0002-9297(08)00589-2
↑ Zhu X, Cruz VE, Zhang H, Erzberger JP, Mendell JT. Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes. Science. 2024 Nov 22;386(6724):eadq8587. PMID:39571015 doi:10.1126/science.adq8587