Search bioRxiv⌕ Search

Biology subjects

Nogimori, T.

Publications and source records attributed to Nogimori, T..

2 recordsLinked to original sources

Neutralizing antibody responses and cellular responses against severe acute respiratory syndrome coronavirus 2 omicron subvariant BA.5 after an mRNA severe acute respiratory syndrome coronavirus 2 vaccine dose in kidney transplant recipients

We examined the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein IgG antibody and neutralizing antibody titers and cellular immunity in 73 uninfected recipients and 17 uninfected healthy controls who received three doses of a coronavirus 2019 mRNA vaccine. Neutralizing antibody titers were evaluated using GFP-carrying recombinant SARS-CoV-2 with spike protein of B.1.1, omicron BA.1, or BA.5. For cellular immunity, peripheral blood mononuclear cells were stimulated with peptides corresponding to spike protein antigens of B.1.1, BA.1, and BA.5; spike-specific CD4/CD8 memory T cells were evaluated using intracellular cytokine staining. The median IgG antibody titers were 7.8 AU/mL in recipients and 143.0 AU/mL in healthy controls (p < 0.0001). Neutralizing antibody titers against all three viral variants were significantly lower in recipients (p < 0.0001). The number of spike-specific CD8 + memory T cells significantly decreased in recipients (p < 0.0001). Twenty recipients and seven healthy controls additionally received a bivalent omicron-containing booster vaccine, and IgG antibody and neutralizing antibody titers increased in both groups; however, the increase was significantly lower in recipients. Recipients did not gain sufficient immunity with a third dose of vaccine, suggesting a need to explore methods other than vaccines.

immunology↗

LARP1 facilitates translational recovery after amino acid refeeding by preserving long poly(A)-tailed TOP mRNAs

Occasionally, cells must adapt to an inimical growth conditions like amino acid starvation (AAS) by downregulating protein synthesis. A class of transcripts containing 5terminal oligopyrimidine (5TOP) motif encodes translation-related proteins such as ribosomal proteins (RPs) and elongation factors, and therefore, their translation is severely repressed during AAS to conserve energy1. The RNA-binding protein LARP1 transduces amino acid signaling to TOP gene expression by controlling translation and stability of TOP mRNAs2-6. When released from AAS, translation machineries in turn have to be restored, however, the underlying mechanism of such re-adaptation is largely unknown. Here we show that LARP1 preserves TOP mRNAs in a long polyadenylated state during long-term AAS. We found that TOP mRNAs become highly polyadenylated when cells are in AAS or treated with the mTOR (mechanistic target of rapamycin) inhibitor Torin1. Importantly, depletion of LARP1 completely abrogated the polyadenylation of TOP mRNAs. Comprehensive analysis of poly(A) tail length using the Nanopore direct RNA sequencing revealed that TOP mRNAs are selectively polyadenylated under mTOR inhibition. Since a long poly(A) tail confers increased stability and polysome formation of TOP mRNAs, we predict that LARP1-dependent preservation of TOP mRNAs enables rapid translational resumption after the release from AAS.

molecular biology↗