Impact of the Multiple Sclerosis-Associated Genetic Variant Gly307Ser on Human CD8 T-Cell Functions.

Background And Objectives: The rs763361 nonsynonymous variant in the gene, which results in a glycine-to-serine substitution at position 307 of the CD226 protein, has been implicated as a risk factor of various immune-mediated diseases, including multiple sclerosis (MS). Compelling evidence suggests that this allele may play a significant role in predisposing individuals to MS by decreasing the immune-regulatory capacity of Treg cells and increasing the proinflammatory potential of effector CD4 T cells. However, the impact of this CD226 gene variant on CD8 T-cell functions, a population that also plays a key role in MS, remains to be determined.

The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis.

Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown.

The splicing regulators TIA1 and TIAL1 are required for the expression of the DNA damage repair machinery during B cell lymphopoiesis.

B cell lymphopoiesis requires dynamic modulation of the B cell transcriptome for timely coordination of somatic mutagenesis and DNA repair in progenitor B (pro-B) cells. Here, we show that, in pro-B cells, the RNA-binding proteins T cell intracellular antigen 1 (TIA1) and TIA1-like protein (TIAL1) act redundantly to enable developmental progression. They are global splicing regulators that control the expression of hundreds of mRNAs, including those involved in DNA damage repair.

MLL4 mediates differentiation and tumor suppression through ferroptosis.

The epigenetic regulator, (), has been described as an essential gene in both humans and mice. In addition, it is one of the most commonly mutated genes in all of cancer biology. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression.