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Article Dans Une Revue Scientific Reports Année : 2019

The interactome analysis of the Respiratory Syncytial Virus protein M2-1 suggests a new role in viral mRNA metabolism post- transcription

Résumé

Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic polyA-binding protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription. Human respiratory syncytial virus (RSV) is the most common cause of respiratory infection in neonates and infants worldwide. Globally, RSV is estimated to cause 33 million cases of acute respiratory illness in children under 5 years of age, resulting in 3.2 million hospital admissions and 118 200 child deaths a year, mostly in developing countries 1. Moreover, RSV infections in adults are increasingly associated with substantial morbidity and mortality in the elderly or at risk population, such as asthmatic and immunocompromised patients 2. RSV belongs to the pneumoviridae family of the Mononegavirales order 3. Its genome consists of a single-strand negative-sense RNA tightly encapsidated by the nucleoprotein N 4. Viral transcription and replication occur in the cytoplasm of infected cells, in virally induced cytoplasmic inclusions called inclusion bodies (IBs) 5-7. Replication is achieved by the viral RNA dependent RNA polymerase L and its cofactor the phosphoprotein P 8. Viral transcription requires an additional viral protein, M2-1 9. The complex formed by L, P and M2-1 proceeds to the sequential transcription of RSV genes by a start and stop mechanism, producing capped and polyadenylated viral mRNAs 8. M2-1 ensures the polymerase processivity both intra-and inter-genically, preventing the synthesis of shortened mRNA and enabling transcription of downstream genes 9-11. M2-1 is composed of four 194 amino acid chains forming a stable homo-tetrameric protein 12,13. Each M2-1 monomer encompasses a zinc finger domain (aa 7-25) at the N terminal extremity, an α helical oligomerization domain (aa 32-49) and a large globular core
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Dates et versions

hal-02907594 , version 1 (27-07-2020)

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Camille Bouillier, Gina Cosentino, Thibaut Leger, Vincent Rincheval, Charles-Adrien Richard, et al.. The interactome analysis of the Respiratory Syncytial Virus protein M2-1 suggests a new role in viral mRNA metabolism post- transcription. Scientific Reports, 2019, 9 (1), ⟨10.1038/s41598-019-51746-0⟩. ⟨hal-02907594⟩
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