TY - JOUR

T1 - Stress-granules, P-bodies, and cell aging: A bioinformatics study

AU - Мокин, Я. И.

AU - Ильинский, Н. С.

AU - Нестеров, С. В.

AU - Смирнов, Е.Я.

AU - Сергеева, О. С.

AU - Романович, Анна Эдуардовна

AU - Кузнецова, И. М.

AU - Туроверов, Константин

AU - Фонин, А В

AU - Уверский, В.Н.

N1 - Stress-granules, P-bodies, and cell aging: A bioinformatics study / Mokin Y. I., Ilyinsky N. S., Nesterov S. V. [et al.] // Biochem Biophys Res Commun. –2024. – V. 694. – 149404. doi: 10.1016/j.bbrc.2023.149404. Epub 2023 Dec 21. PMID: 38147698.

PY - 2024/1/29

Y1 - 2024/1/29

N2 - Abstract: At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-lessorganelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in theproteome 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 shownthat the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consistsof completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquidliquidphase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS isrelatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-lessorganelles. Proteins whose gene expression changes during the transition of human cells to a senescent statemake up about 20% of the studied proteomes. There is a statistically significant increase in the number ofpositively 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 stressgranulesdataset with senescence-related processes. Among SG proteins potentially involved in senescentprocesses, there is an increase in the abundance of potentially amyloidogenic proteins compared to the wholeproteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS amongsuch 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 largestcluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. Thesedata indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state ofMLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

AB - Abstract: At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-lessorganelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in theproteome 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 shownthat the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consistsof completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquidliquidphase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS isrelatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-lessorganelles. Proteins whose gene expression changes during the transition of human cells to a senescent statemake up about 20% of the studied proteomes. There is a statistically significant increase in the number ofpositively 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 stressgranulesdataset with senescence-related processes. Among SG proteins potentially involved in senescentprocesses, there is an increase in the abundance of potentially amyloidogenic proteins compared to the wholeproteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS amongsuch 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 largestcluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. Thesedata indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state ofMLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

KW - liquid-liquid phase separation; membrane-less organelles; stress granules; P-bodies; intrinsically disordered proteins; intrinsically disordered regions; aging; senescence; protein aggregation; nucleic acids; RNA-binding protein; DNA-binding protein

KW - Aging

KW - DNA-Binding protein

KW - Intrinsically disordered proteins

KW - Intrinsically disordered regions

KW - Liquid-liquid phase separation

KW - Membrane-less organelles

KW - Nucleic acids

KW - P-bodies

KW - Protein aggregation

KW - RNA-Binding protein

KW - Senescence

KW - Stress granules

UR - https://www.mendeley.com/catalogue/c499e6b7-3306-3e59-bdc0-4d03738481ad/

U2 - 10.1016/j.bbrc.2023.149404

DO - 10.1016/j.bbrc.2023.149404

M3 - Article

VL - 694

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -