Major histocompatibility complex class II mRNAs encode heterodimeric proteins involved in the presentation of exogenous antigens during an immune response. Their 3'UTRs bind a protein complex in which we identified two factors: EBP1, an ErbB3 receptor-binding protein and DRBP76, a double-stranded RNA binding nuclear protein, also known as nuclear factor 90 (NF90). Both are well-characterized regulatory factors of several mRNA molecules processing. Using either EBP1 or DRBP76/NF90-specific knockdown experiments, we established that the two proteins play a role in regulating the expression of HLA-DRA, HLA-DRB1 and HLA-DQA1 mRNAs levels. Our study represents the first indication of the existence of a functional unit that includes different transcripts involved in the adaptive immune response. We propose that the concept of 'RNA operon' may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3'UTR with same proteins.
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http://dx.doi.org/10.1093/nar/gkr278 | DOI Listing |
Nat Cancer
January 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
Recombinant adeno-associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex.
View Article and Find Full Text PDFSci China Life Sci
January 2025
State Key Laboratory of Genetic Engineering, Lab for Evolutionary Synthesis, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Human leukocyte antigen (HLA) genes in the major histocompatibility complex (MHC) region are crucial for immunity and are associated with numerous diseases and phenotypes. The MHC region's complexity and high genetic diversity make it challenging to analyze using short-read sequencing (SRS) technology. We sequence the MHC region of 100 Han Chinese individuals using both long-read sequencing (LRS) and SRS platforms at approximately 30X coverage to study genetic alterations and their potential functional impacts.
View Article and Find Full Text PDFCell Death Dis
January 2025
Department of Pathology, The Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
Approximately 80% of nasopharyngeal carcinoma (NPC) patients exhibit EGFR overexpression. The overexpression of EGFR has been linked to its potential role in modulating major histocompatibility complex class I (MHC-I) molecules. We discovered that EGFR, operating in a kinase-independent manner, played a role in stabilizing the expression of SLC7A11, which subsequently inhibited MHC-I antigen presentation.
View Article and Find Full Text PDFAm J Transplant
January 2025
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address:
Pre-transplantation HLA antibody testing is necessary to assess compatibility between donor and recipient pairs. Over the past decade, the virtual crossmatch (VXM) has replaced the physical crossmatch (PXM) as the main assessment of pre-transplant histocompatibility. At our center, most transplants have proceeded based solely on the VXM, followed by a retrospective PXM.
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