A two-faced protein enables RNA-mediated DNA repair

By: James V. Kohl | Published on: November 29, 2015

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…is the god of beginnings and transitions,^[1] and thereby of gates, doors, doorways, passages and endings. He is usually depicted as having two faces, since he looks to the future and to the past.

My comment: Nutrient-dependent beginnings of morphological and behavioral diversity are biophysically constrained by the physiology of species-specific RNA-mediated DNA repair in the context of reproduction.

Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains

Excerpt:

Despite barely conserved primary sequences (Supplementary Fig. 5b), we noted that 109–139 amino acids of the Sesn-A domain show a very distant sequence homology to YP_296737.1 as well as to AhpD, a well-characterized alkylhydroperoxidase in Mycobacterium tuberculosis^{21, 22, 23}, as formerly reported². The homology region corresponds to the helix–turn–helix motif of AhpD, a signature motif found in the family of AhpD-like oxidoreductases^{21, 22, 23}. The relative position of the motif within the primary sequence is similar between hSesn2 and YP_296737.1 but different in AhpD (Supplementary Fig. 5a). Interestingly, whereas both YP_296737.1 and AhpD are characterized by a catalytic cysteine dyad (Cys86 and Cys89 in YP_296737.1), the Sesn-A domain contains only the first cysteine (Cys125 in hSesn2) with the second cysteine being substituted for a leucine (Leu128 in hSesn2) (Fig. 2b).

Reported as: Dual role of stress-inducible metabolic regulators

Excerpt:

While the N-terminal domain (Sesn-A) reduces alkylhydroperoxide radicals through its helix–turn–helix oxidoreductase motif, the C-terminal domain (Sesn-C) modified this motif to accommodate physical interaction with GATOR2 and subsequent inhibition of mTORC1.

These findings clarify the c of how Sestrins can attenuate degenerative processes such as aging and diabetes by acting as a simultaneous inhibitor of ROS accumulation and mTORC1 activation.

My comment: All nutrient-dependent RNA-mediated events can be viewed in this context.

See: The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1

My comment: Nutrient-sensing mechanisms are biophysically constrained by the de novo creation of receptors that allow nutrients to enter cells and by the physiology of RNA-mediated gene duplication and RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera in the context of their physiology of reproduction. The molecular mechanisms that link ecological variation to ecological adaptations are confusing to anyone who tries to place them into the context of neo-Darwinian theories about mutations and evolution. The molecular mechanisms link atoms to ecosystems via microRNAs, adhesion proteins, and supercoiled DNA, which protects organized genomes from virus-driven entropy.