Transcripts coding MHC I-associated peptides are enriched in microRNA-binding sites

ABSTRACT: MHC I-peptides (MIPs) play an essential role in normal homeostasis and diverse pathological conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and whose physical nature remains elusive. We used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and -B molecules on human EBV-infected B lymphocytes from four subjects. We found that although HLA-different subjects present different MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biological pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved vs. polymorphic genomic sequences, derived preferentially from abundant transcripts and conveyed to the cell surface a cell type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, while MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which i) the generation of MIPs by a transcript depends on its abundance and DRiP rate, and ii) the DRiP rate is regulated to a large extent by miRNAs. We performed genome-wide miRNA expression profiling of B cells and non-lymphoid cells to confirm that miRNAs predicted to regulate transcripts source of MHC I-associated peptides are expressed in a cell-specific manner. miRNA profiling was done on (i) 4 B-lymphoblastoid cell lines (B-LCLs) obtained from the peripheral blood mononuclear cells of 4 subjects, (ii) CD19+CD20- B cells and CD19+CD20+ B cells of one of the subjects, (iii) HeLa cells, and (iv) HEK293 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Diana Granados 

PROVIDER: E-GEOD-35319 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress