The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation

Abstract

Alternative splicing of pre-mRNA helps to enhance the genetic diversity within mammalian cells by increasing the number of protein isoforms that can be generated from one gene product. This provides a great deal of flexibility to the host cell to alter protein function, but when dysregulation in splicing occurs this can have important impact on health and disease. Alternative splicing is widely used in the mammalian immune system to control the development and function of antigen specific lymphocytes. In this review we will examine the splicing of pre-mRNAs yielding key proteins in the immune system that regulate apoptosis, lymphocyte differentiation, activation and homeostasis, and discuss how defects in splicing can contribute to diseases. We will describe how disruption to trans-acting factors, such as heterogeneous nuclear ribonucleoproteins (hnRNPs), can impact on cell survival and differentiation in the immune system.

Genome‐wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1

“…In human, lncRNAs are known to play a major role in gene regulation, including the regulation of alternative splicing and their dysfunction may have an impact on several pathologies and diseases (Fernandes, Acuña, Aoki, Floeter‐Winter, & Muxel, ; Romero‐Barrios, Legascue, Benhamed, Ariel, & Crespi, ). Alternative splicing is prevalent in the mammalian immune system to control lymphocyte homeostasis (Yabas, Elliott, & Hoyne, ). Moreover, lncRNAs regulate the inflammatory response following activation of innate immunity and have been related to autoimmune diseases such as psoriasis (Ahn et al, ; Heward & Lindsay, ).…”

Comparative proteomic analysis reveals different responses in porcine lymph nodes to virulent and attenuated homologous African swine fever virus strains

“…Of particular interest could be the complex regulation found for several members of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex, RNA-binding proteins involved in downstream gene regulation and G2/M DNA damage checkpoint regulation, apoptosis and immune regulation [38]. hnRNPH1, a protein previously shown as being involved in virus replication [39], was upregulated at day 1 pi with both viruses, overexpression that was maintained for the attenuated E75CV1 virus at day 3 and 7 pi.…”

The Characterization of GSDMB Splicing and Backsplicing Profiles Identifies Novel Isoforms and a Circular RNA That Are Dysregulated in Multiple Sclerosis

“…More than 95% of human genes undergo AS [5], implicating a role of this mechanism in all cellular processes. Indeed, AS concerns a vast number of genes involved in many immune system functions, such as T-cell activation and migration, cytokine response, and T-cell homeostasis and apoptosis, all being crucial to prevent the breakdown of self-tolerance and the development of autoimmunity [6,7]. It has been also suggested that AS may increase the immunogenicity of autoantigens by creating novel epitopes that might break the immune tolerance [8].…”