Genome complexity: product controls (Introduction)

by David Turell , Friday, November 27, 2020, 14:52 (1239 days ago) @ David Turell

The finding of genome complexity is a bottomless pit of never ending steps of control:

https://science.sciencemag.org/content/370/6520/1105

"Human mitochondria have their own genome and ribosomes called mitoribosomes that respectively encode and synthesize essential subunits of complexes that use the energy from the oxidation of metabolites to drive the synthesis of adenosine triphosphate (ATP). These complexes are key to the health of the cell. Desai et al. studied a mitoribosome-associated quality control pathway that prevents aberrant translation. They purified mitoribosomes under conditions designed to induce stalling and determined the structures of two intermediates in the rescue pathway. These structures revealed two proteins that eject the unfinished polypeptide chain and peptidyl transfer RNA from the ribosome. Their cryo–electron microscopy dataset also revealed additional states that may correspond to intermediates in the mitochondrial translation elongation cycle. (my bold)

"Abstract
The human mitochondrial ribosome (mitoribosome) and associated proteins regulate the synthesis of 13 essential subunits of the oxidative phosphorylation complexes. We report the discovery of a mitoribosome-associated quality control pathway that responds to interruptions during elongation, and we present structures at 3.1- to 3.3-angstrom resolution of mitoribosomal large subunits trapped during ribosome rescue. Release factor homolog C12orf65 (mtRF-R) and RNA binding protein C6orf203 (MTRES1) eject the nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for these factors during mitoribosome rescue. We also report related cryo–electron microscopy structures (3.7 to 4.4 angstrom resolution) of elongating mitoribosomes bound to tRNAs, nascent polypeptides, the guanosine triphosphatase elongation factors mtEF-Tu and mtEF-G1, and the Oxa1L translocase.

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"A paradigm shift occurred in the field of translation when it was discovered that cells use the translation machinery itself to detect errors and activate quality control mechanisms. Although the existence of quality control in mitochondria was predicted on the basis of analogy with bacteria and eukaryotic cytosol, very little was known about the molecular mechanisms. Our discovery of a mitoribosome-associated quality control pathway and structural characterization of elongating mitoribosomes now set the stage to understand the regulation of mitochondrial translation. We also demonstrate that exhaustive in silico classification of large cryo-EM datasets can serve as a viable alternative strategy to uncover processes involved in translation in the absence of suitable in vitro tools."

Comment: This last paragraph discusses the many levels of quality control that exist. My bold in the first paragraph indicates how important this control really is. It indicates the level of concern the designer had.