LARP1 binds SARS-CoV-2 RNA

Stable Identifier
R-HSA-9760510
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol, double membrane vesicle viral factory outer membrane
ReviewStatus
5/5
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LARP1 binds SARS-CoV-2 RNA
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La-related protein 1 (LARP1) binds the 7-methylguanosine triphosphate (m7Gppp) cap and adjacent 5’-terminal oligopyrimidine (5’TOP) motif of 5'TOP-bearing mRNAs that encode components of ribosome biogenesis (Tcherkezian J et al. 2014; Lahr RM et al. 2017). LARP1 can also bind to 3' terminus of poly(A) mRNA (Aoki K et al. 2013; Mattijssen S et al. 2021; Al-Ashtal HA et al. 2021). LARP1 regulates 5'TOP mRNA translation downstream of mTOR complex 1 (mTORC1) thus linking mTORC1 signalling to ribosome biogenesis (Fonseca BD et al. 2015; Tcherkezian J et al. 2014; Hong S et al. 2015; Lahr RM et al. 2017). Upon mTORC1 inhibition LARP1 has increased affinity for 5′TOP mRNAs (Fonseca BD et al. 2015), whereas mTORC1-mediated phosphorylation of LARP1 impairs RNA binding and regulatory function of LARP1 (Hong S et al. 2015; Jia JJ et al. 2021). LARP1 regulates 5'TOP mRNA translation via the C-terminal DM15 region (Lahr RM et al. 2017). It remains controversial whether LARP1 functions as a translation repressor (Fonseca BD et al. 2015; Lahr RM et al. 2017; Philippe L et al. 2018, 2020) or stabilizer of 5'TOP mRNAs (Aoki K et al. 2013; Tcherkezian J et al. 2014; reviewed in Berman AJ et al. 2021).

As an RNA-binding protein LARP1 was identified in the interactome of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) RNA (Schmidt N et al. 2021; Lee S et al. 2021; Flynn RA et al. 2021). Enhanced crosslinking and immunoprecipitation (eCLIP) data suggest that LARP1 may interact with pyrimidine-rich sites within SARS-CoV-2 RNA (Schmidt N et al. 2021). LARP1 deficiency in SARS-CoV-2-infected human embryonic kidney (HEK293) cells and human lung cancer (Calu-3) cells resulted in elevated levels of intracellular viral RNA (Schmidt N et al. 2021; Lee S et al. 2021). Contrarily, overexpression of LARP1 led to a reduction of viral growth. These data suggest that LARP1 functions as an antiviral host factor (Schmidt N et al. 2021; Lee S et al. 2021).

This Reactome event shows LARP1 binding to SARS-CoV-2 5'RNA.

Literature References
PubMed ID Title Journal Year
33989516 The SARS-CoV-2 RNA interactome

Son, A, Lee, S, Choi, Y, Kim, JS, Lee, KM, Lee, YS, Kim, VN, Kim, J, Park, Y

Mol Cell 2021
33349665 The SARS-CoV-2 RNA-protein interactome in infected human cells

Ade, J, Schneider, C, Zimmer, M, Lareau, CA, Ganskih, S, Bodem, J, Wei, Y, Kirschner, L, Zielinski, S, Hennig, T, Keshishian, H, Munschauer, M, Carr, SA, Schmidt, N, Caliskan, N, Melanson, R, Werner, S, Vogel, J, Lander, ES, Dölken, L, Fischer, U

Nat Microbiol 2021
Participants
Input
Output
Participates
as an event of
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-12-18)
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