Selection of start codon during mRNA scanning in eukaryotic translation initiation. 2022

Ipsita Basu, and Biswajit Gorai, and Thyageshwar Chandran, and Prabal K Maiti, and Tanweer Hussain
Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bangalore, 560012, India.

Accurate and high-speed scanning and subsequent selection of the correct start codon are important events in protein synthesis. Eukaryotic mRNAs have long 5' UTRs that are inspected for the presence of a start codon by the ribosomal 48S pre-initiation complex (PIC). However, the conformational state of the 48S PIC required for inspecting every codon is not clearly understood. Here, atomistic molecular dynamics (MD) simulations and energy calculations suggest that the scanning conformation of 48S PIC may reject all but 4 (GUG, CUG, UUG and ACG) of the 63 non-AUG codons, and initiation factor eIF1 is crucial for this discrimination. We provide insights into the possible role of initiation factors eIF1, eIF1A, eIF2α and eIF2β in scanning. Overall, the study highlights how the scanning conformation of ribosomal 48S PIC acts as a coarse selectivity checkpoint for start codon selection and scans long 5' UTRs in eukaryotic mRNAs with accuracy and high speed.

UI MeSH Term Description Entries
D010442 Peptide Chain Initiation, Translational A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis. Chain Initiation, Peptide, Translational,Protein Biosynthesis Initiation,Protein Chain Initiation, Translational,Protein Translation Initiation,Translation Initiation, Genetic,Translation Initiation, Protein,Translational Initiation, Protein,Translational Peptide Chain Initiation,Biosynthesis Initiation, Protein,Genetic Translation Initiation,Initiation, Genetic Translation,Initiation, Protein Biosynthesis,Initiation, Protein Translation,Initiation, Protein Translational,Protein Translational Initiation
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015977 Eukaryotic Initiation Factor-1 A eukaryotic initiation factor that binds to 40S ribosomal subunits. Although initially considered a "non-essential" factor for eukaryotic transcription initiation, eukaryotic initiation factor-1 is now thought to play an important role in localizing RIBOSOMES at the initiation codon of MRNA. EIF-1,Peptide Initiation Factor EIF-1,Eukaryotic Peptide Initiation Factor-1,Eukaryotic Initiation Factor 1,Eukaryotic Peptide Initiation Factor 1,Peptide Initiation Factor EIF 1
D018387 Codon, Initiator A codon that directs initiation of protein translation (TRANSLATION, GENETIC) by stimulating the binding of initiator tRNA (RNA, TRANSFER, MET). In prokaryotes, the codons AUG or GUG can act as initiators while in eukaryotes, AUG is the only initiator codon. Codon, Start,Initiator Codon,Codon, Initiation,Start Codon,Codons, Initiation,Codons, Initiator,Codons, Start,Initiation Codon,Initiation Codons,Initiator Codons,Start Codons
D020121 5' Untranslated Regions The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences. 5'UTR,Leader Sequences, mRNA,Leader mRNA Sequences,mRNA Leader Sequences,5' UTR,5' UTRs,5' Untranslated Region,5'UTRs,Leader Sequence, mRNA,Leader mRNA Sequence,Region, 5' Untranslated,Regions, 5' Untranslated,Sequence, Leader mRNA,Sequence, mRNA Leader,Sequences, Leader mRNA,Sequences, mRNA Leader,UTR, 5',UTRs, 5',Untranslated Region, 5',Untranslated Regions, 5',mRNA Leader Sequence,mRNA Sequence, Leader,mRNA Sequences, Leader

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