RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication

Brugier, Alexis; Hafirrassou, Mohamed Lamine; Pourcelot, Marie; Baldaccini, Morgane; Kril, Vasiliya; Couture, Laurine; Kümmerer, Beate M.; Gallois-Montbrun, Sarah; Bonnet-Madin, Lucie; Vidalain, Pierre‐Olivier; Delaugerre, Constance; Pfeffer, Sébastien; Meertens, Laurent; Amara, Ali

doi:10.1128/jvi.01962-21

Cited by 21 publications

(18 citation statements)

References 59 publications

(83 reference statements)

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“…This may offer additional insight into the reduced egg production observed in dehydrated mosquitoes [ 7 ], or potentially into the veiled 20-hydroxyecdysone (20E) signaling pathway. Another over-expressed gene of interest identified in our Y1_Y7 comparison, vigilin (AAEL001421-RA), has been implicated in the formation of RACK1, which is involved in viral RNA binding for DENV genome amplification [ 65 ]. Considering the abundance of RNA-involved processes in our Y7_N7 comparison, especially regarding our Y1_N1 comparison, possibilities exist for interactions between imbibed pathogens and the genes expressed within dehydrated mosquitoes.…”

Section: Discussionmentioning

confidence: 99%

Dehydration Alters Transcript Levels in the Mosquito Midgut, Likely Facilitating Rapid Rehydration following a Bloodmeal

Holmes

Brown

Sharma

et al. 2023

Insects

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The mosquito midgut is an important site for bloodmeal regulation while also acting as a primary site for pathogen exposure within the mosquito. Recent studies show that exposure to dehydrating conditions alters mosquito bloodfeeding behaviors as well as post-feeding regulation, likely altering how pathogens interact with the mosquito. Unfortunately, few studies have explored the underlying dynamics between dehydration and bloodmeal utilization, and the overall impact on disease transmission dynamics remains veiled. In this study, we find that dehydration-based feeding in the yellow fever mosquito, Aedes aegypti, prompts alterations to midgut gene expression, as well as subsequent physiological factors involving water control and post-bloodfeeding (pbf) regulation. Altered expression of ion transporter genes and aquaporin 2 (AQP2) in the midgut of dehydrated mosquitoes as well as the rapid reequilibration of hemolymph osmolality after a bloodmeal indicate an ability to expedite fluid and ion processing. These alterations ultimately indicate that female A. aegypti employ mechanisms to ameliorate the detriments of dehydration by imbibing a bloodmeal, providing an effective avenue for rehydration. Continued research into bloodmeal utilization and the resulting effects on arthropod-borne transmission dynamics becomes increasingly important as drought prevalence is increased by climate change.

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Section: Discussionmentioning

confidence: 99%

Dehydration Alters Transcript Levels in the Mosquito Midgut, Likely Facilitating Rapid Rehydration following a Bloodmeal

Holmes

Brown

Sharma

et al. 2023

Insects

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show abstract

“…For instance, the aforementioned interactors, components of the eIF3 complex and CSDE1, are both implicated in IRES-mediated viral translation in a variety of viruses (91–93). SERBP1 itself has also recently been shown to interact with dengue virus RNA and regulate its translation (94). Finally, we observed a significant overlap between SERBP1-associated proteins and the SARS-CoV-2 interactome, with 82 proteins out of 145 shared interactors being involved in translation.…”

Section: Discussionmentioning

confidence: 99%

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Breunig,

Lei,

Montalbano

et al. 2024

Preprint

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RNA binding proteins (RBPs) containing intrinsically disordered regions (IDRs) are present in diverse molecular complexes where they function as dynamic regulators. Their characteristics promote liquid-liquid phase separation (LLPS) and the formation of membraneless organelles such as stress granules and nucleoli. IDR-RBPs are particularly relevant in the nervous system and their dysfunction is associated with neurodegenerative diseases and brain tumor development. SERBP1 is a unique member of this group, being mostly disordered and lacking canonical RNA-binding domains. Using a proteomics approach followed by functional analysis, we defined SERBP1’s interactome. We uncovered novel SERBP1 roles in splicing, cell division, and ribosomal biogenesis and showed its participation in pathological stress granules and Tau aggregates in Alzheimer’s disease brains. SERBP1 preferentially interacts with other G-quadruplex (G4) binders, implicated in different stages of gene expression, suggesting that G4 binding is a critical component of SERBP1 function in different settings. Similarly, we identified important associations between SERBP1 and PARP1/polyADP-ribosylation (PARylation). SERBP1 interacts with PARP1 and its associated factors and influences PARylation. Moreover, protein complexes in which SERBP1 participates contain mostly PARylated proteins and PAR binders. Based on these results, we propose a feedback regulatory model in which SERBP1 influences PARP1 function and PARylation, while PARylation modulates SERBP1 functions and participation in regulatory complexes.

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“…This may offer additional insight into the reasons behind reduced egg production observed in dehydrated mosquitoes [7], or potentially into the veiled 20-hydroxyecdysone (20E) signaling pathway. Another over-expressed gene of interest identified in our Y1_Y7 comparison, vigilin (AAEL001421-RA), has been implicated in the formation of RACK1, which is involved in viral RNA binding for DENV genome amplification [59]. Considering the abundance of RNA-involved processes in our Y7_N7 comparison, especially regarding our Y1_N1 comparison, possibilities exist for interactions between imbibed pathogens and the genes expressed within dehydrated mosquitoes.…”

Section: Discussionmentioning

confidence: 99%

Dehydration alters transcript levels in the mosquito midgut, likely facilitating rapid rehydration

Holmes

Brown

Sharma

et al. 2022

Preprint

View full text Add to dashboard Cite

The mosquito midgut is an important site for bloodmeal regulation while also acting as a primary site for pathogen exposure within the mosquito. Recent studies show that exposure to dehydrating conditions alters mosquito bloodfeeding behaviors as well as post-feeding regulation, likely altering how pathogens interact with the mosquito. Unfortunately, few studies have explored the underlying dynamics between dehydration and bloodmeal utilization, and the overall impact on disease transmission dynamics remains veiled. In this study, we find that dehydration-based feeding in the yellow fever mosquito, Aedes aegypti, prompts alterations to midgut gene expression, as well as subsequent physiological factors involving water control and post-bloodfeeding (pbf) regulation. Altered expression of ion transporter genes in the midgut of dehydrated mosquitoes and rapid reequilibration of hemolymph osmolality after a bloodmeal indicate an ability to expedite fluid and ion processing. These alterations ultimately indicate that female A. aegypti employ mechanisms to ameliorate the detriments of dehydration by imbibing a bloodmeal, providing an effective avenue for rehydration. Continued research into bloodmeal utilization and the resulting effects on arthropod-borne transmission dynamics becomes increasingly important as drought prevalence is increased by climate change.

show abstract

RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication

Cited by 21 publications

References 59 publications

Dehydration Alters Transcript Levels in the Mosquito Midgut, Likely Facilitating Rapid Rehydration following a Bloodmeal

Dehydration Alters Transcript Levels in the Mosquito Midgut, Likely Facilitating Rapid Rehydration following a Bloodmeal

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Dehydration alters transcript levels in the mosquito midgut, likely facilitating rapid rehydration

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