6/18/2023 0 Comments Snapgene alternative![]() Generating multiple chemerin isoforms is critical for controlling its local and context-specific bioactivity. The mChem162K and hChem163S proteins are the major chemerin forms present in mouse and human plasma, respectively. While in humans, only a single transcript (NM_002889.4) encoding a 163 amino acid (aa) protein has been described, in the mouse, three alternatively spliced transcripts (NM_001347168.1, NM_027852.3, and NM_001347167.1) encoding 162 or 163 aa proteins have been reported. Both mouse and human RARRES2 genes are comprised of six exons and five introns. While mechanisms of proteolytic processing in generating chemerin isoforms are relatively well described, the role of alternative splicing remains obscure. ![]() ![]() Mouse chemerin undergoes tissue-specific proteolytic cleavage similar to human chemerin. Several murine chemerin isoforms have been characterized in a mouse model of obesity, with mChem156S and mChem155F exhibiting the highest biological activity. Different proteolytic activities can generate isoforms with low or no activity, including 152G, 153Q, 154 F, 155 A, 156 F, and 158 K. The most active form of human chemerin, hChem157S, is produced by direct cleavage of six C-terminal amino acids by neutrophil elastase or cathepsin G. Pro-chemerin is converted to chemotactically active isoforms through posttranslational carboxyl-terminal processing by proteases belonging to the coagulation, fibrinolytic, and inflammatory cascades. Ĭhemerin is secreted as pro-chemerin, a functionally inert precursor protein called hChem163S (human) and mChem162K (mouse), where the number and capital letter indicate the terminal amino acid position and code, respectively. Nevertheless, RARRES2 mRNA is present in other tissues, including the adrenal glands, ovaries, pancreas, lungs, kidneys, and skin Chemerin-induced signaling is mediated predominantly through chemokine-like receptor 1 (CMKLR1), which is expressed by many cells, including hepatocytes, adipocytes, keratinocytes, plasmacytoid dendritic cells (pDCs), and macrophages. Liver and adipose tissue are reportedly the major sites of chemerin production. The gene encoding chemerin is called retinoic acid receptor responder 2 ( RARRES2) or tazarotene-induced gene 2 ( TIG2). Ĭhemerin is a multifunctional chemoattractant, adipokine, and antimicrobial agent that regulates different biological processes, including immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, glucose homeostasis, and microbial growth. Therefore, discovering novel mRNA transcripts and protein isoforms can uncover new biological roles and functions of genes. Despite sharing a high degree of amino acid sequence homology, each isoform can have various, even opposite, biological roles. However, the alternative splicing of transcripts is one of the main sources of proteomic diversity in eukaryotes. Alternative polyadenylation, RNA editing, and posttranslational modification can also create functionally distinct proteins. They can originate from separate genes, or a single gene can code for multiple proteins through alternative mRNA splicing. Protein isoforms can play important roles in various biological processes, such as growth, differentiation, and signal transduction. Our findings indicate a limited role for alternative splicing in generating chemerin isoform diversity under all tested conditions. However, only one transcript variant of human RARRES2 was present in liver and adipose tissue. Moreover, analyses of real-time quantitative PCR (RT-qPCR) and publicly-available next-generation RNA sequencing (RNA-seq) datasets showed that different alternatively spliced variants of mouse Rarres2 are present in mouse tissues and their expression patterns were unaffected by inflammatory and infectious stimuli except brown adipose tissue. Using rapid amplification of cDNA ends (RACE) PCR, we determined RARRES2 transcript variants present in mouse and human tissues and identified novel transcript variant 4 of mouse Rarres2 encoding mChem153K. While these mechanisms are relatively well known, the role of alternative splicing in generating isoform diversity remains obscure. Chemerin bioactivity largely depends on carboxyl-terminal proteolytic processing that generates chemerin isoforms with different chemotactic, regulatory, and antimicrobial potentials. Chemerin is a chemoattractant protein with adipokine and antimicrobial properties encoded by the retinoic acid receptor responder 2 ( RARRES2) gene.
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