2'O-ribose methylation of ribosomal RNA (rRNA 2'Ome) in primary human T cells from septic shock and COVID-19 patients

Abstract

T cell exhaustion plays a central role in sepsis-induced immunosuppression. Deciphering the precise mechanism of this cellular dysfunction could lead to new therapies. In several pathophysiological contexts, the 2’O-ribose methylation of ribosomal RNA (rRNA 2’Ome) has emerged as a level of epitranscriptomic regulation. Here, we report for the first time site-specific alterations of rRNA 2’Ome epitranscriptomic marks in T cells after sepsis, associated with impaired functionality. Using primary human T cells from septic shock and COVID-19 patients, we identified a subset of sites with high inter-individual variability, the levels of which correlated with lymphocyte effector functions. This was recapitulated in an ex vivo model of stimulated T lymphocytes from healthy donors. Finally, 2’Ome signature discriminated samples from septic patients from those of healthy donors. We describe rRNA 2’Ome regulation as a new molecular mechanism that controls T lymphocyte effector function in sepsis with high potential as biomarker and therapeutic target. 

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Description of the data and file structure

Each folder contains the read-end counts in the sub-directory RiboMethSeq_ReadEnd_Counts and the metadata file. The metadata file describe each file contained in this sub-directory.

The read-end count file structure:

The name of the RNA on which the read end counting was performed.

The number of the position on the RNA.

The value of the read end counts at the position.

Code/Software

Using ribomethseq-nf pipeline, fastq were used to align reads on the human rRNA sequence (NR_046235), compute 5’/3’-end read counts.

These files can be the input of rRMSAnalyzer package to adjust batch effect (ComBat-seq method) and calculate C-score corresponding to the end read count at the genomic position of interest normalized to the median of end read counts of the local environment (6 upstream and 6 downstream nucleotides).