Sandbox Reserved 327: Difference between revisions
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eIF1 is essential to control the ribosome conformational rearrangement in translation initiation by stimulating the formation of MFC and controlling the start codon selection which allow the translation elongation process to occur | eIF1 is essential to control the ribosome conformational rearrangement in translation initiation by stimulating the formation of MFC and controlling the start codon selection which allow the translation elongation process to occur | ||
<ref name="eIF1"/><ref name="asano"/>.Start codon selection is a key step for translation elongation to occur because recognition of the right AUG start codon would lead to the binding of 60S subunit to form the 80 S initiation complex, a precursor for elongation <ref name="eIF1"/>. Study showed eIF1 dissociation plays a critical role in start codon selection <ref name="cheung"/>. Initially, eIF1 in the 43S PIC would interact with the 5’end of mRNA to form 48S PIC and promotes scanning until the Met-tRNA<sub>i</sub><sup>Met</sup> recognizes the right AUG codon from the mRNA <ref name="eIF1"/><ref name="cheung"/>. Once the right codon is recognized, there would be a conformational change on the ribosome and the Met-tRNA<sub>i</sub><sup>Met</sup> would be released to the P-site, ready for the elongation process (paper, cheung). Also, hydrolysis of eIF2.GTP to GDP by the action of N-terminal residues of eIF5 in the PIC complex would occur, leading to a Pi being released <ref name="eIF1"/><ref name="cheung"/>. These two events would let the eIF1 and eIF2.GDP to be released from the PIC. Then, eIF5 GTPase would promote the binding of the ribosomal 60S forming the 80S ribosome, get it ready for elongation <ref name="eIF1"/>. The eIF2-GDP is then going to be re-used for another TC formation when it is recycled back to eIF2-GTP by eIF2B.GEF <ref name="eIF1"/>. However, when the codon-anticodon pair is mismatched, eIF1 would avoid the recognition by preventing the hydrolysis through blocking the Pi release at non-AUG codons and repressing the activity of eIF5 GTPase <ref name="eIF1"/><ref name="lomakin"/><ref name="cheung"/>. | <ref name="eIF1"/><ref name="asano"/>.Start codon selection is a key step for translation elongation to occur because recognition of the right AUG start codon would lead to the binding of 60S subunit to form the 80 S initiation complex, a precursor for elongation <ref name="eIF1"/>. Study showed eIF1 dissociation plays a critical role in start codon selection <ref name="cheung"/>. Initially, eIF1 in the 43S PIC would interact with the 5’end of mRNA to form 48S PIC and promotes scanning until the Met-tRNA<sub>i</sub><sup>Met</sup> recognizes the right AUG codon from the mRNA <ref name="eIF1"/><ref name="cheung"/>. Once the right codon is recognized, there would be a conformational change on the ribosome and the Met-tRNA<sub>i</sub><sup>Met</sup> would be released to the P-site, ready for the elongation process (paper, cheung). Also, hydrolysis of eIF2.GTP to GDP by the action of N-terminal residues of eIF5 in the PIC complex would occur, leading to a Pi being released <ref name="eIF1"/><ref name="cheung"/>. These two events would let the eIF1 and eIF2.GDP to be released from the PIC. Then, eIF5 GTPase would promote the binding of the ribosomal 60S forming the 80S ribosome, get it ready for elongation <ref name="eIF1"/>. The eIF2-GDP is then going to be re-used for another TC formation when it is recycled back to eIF2-GTP by eIF2B.GEF <ref name="eIF1"/>. However, when the codon-anticodon pair is mismatched, eIF1 would avoid the recognition by preventing the hydrolysis through blocking the Pi release at non-AUG codons and repressing the activity of eIF5 GTPase <ref name="eIF1"/><ref name="lomakin"/><ref name="cheung"/>. | ||
Mutations in eIF1 would alter the function and mechanism of eIF1 in the cell. There are two classesof mutations in yeast eIF1: ''Mof2'' and ''Sui1'' mutations <ref name="flet"/>. Mof2 mutation in eIF1 would increase the ribosome frameshifting in the translation process <ref name="flet"/>. As for ''Sui1'' mutation, | |||
''in vitro'' and ''in vivo'' mutations would let the mismatched pairing of Met-tRNA<sub>i</sub><sup>Met</sup> with non-AUG codons to occur <ref name="flet"/>. Initiation at UUG codons would be increased instead, while the binding of eIF1 to 40S subunits would be reduced <ref name="cheung"/>. However, this mutation would increase the eIF1 dissociation and Pi release rate from the PIC while another mutation that is completely the opposite, suppress the expression of ''Sui'' mutation (hyperaccuracy mutation in eIF1A), would decrease the dissociation rate <ref name="cheung"/>. | |||
=References= | =References= | ||