Mokin, Y.I.; Ilyinsky, N.S.; Nesterov, S.V.; Smirnov, E.Y.; Sergeeva, O.S.; Romanovich, A.E.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. Stress-Granules, P-Bodies, and Cell Aging: A Bioinformatics Study. Biochemical and Biophysical Research Communications 2024, 694, 149404, doi:10.1016/j.bbrc.2023.149404.
Mokin, Y.I.; Ilyinsky, N.S.; Nesterov, S.V.; Smirnov, E.Y.; Sergeeva, O.S.; Romanovich, A.E.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. Stress-Granules, P-Bodies, and Cell Aging: A Bioinformatics Study. Biochemical and Biophysical Research Communications 2024, 694, 149404, doi:10.1016/j.bbrc.2023.149404.
Mokin, Y.I.; Ilyinsky, N.S.; Nesterov, S.V.; Smirnov, E.Y.; Sergeeva, O.S.; Romanovich, A.E.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. Stress-Granules, P-Bodies, and Cell Aging: A Bioinformatics Study. Biochemical and Biophysical Research Communications 2024, 694, 149404, doi:10.1016/j.bbrc.2023.149404.
Mokin, Y.I.; Ilyinsky, N.S.; Nesterov, S.V.; Smirnov, E.Y.; Sergeeva, O.S.; Romanovich, A.E.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. Stress-Granules, P-Bodies, and Cell Aging: A Bioinformatics Study. Biochemical and Biophysical Research Communications 2024, 694, 149404, doi:10.1016/j.bbrc.2023.149404.
Abstract
At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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