Abstract
Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an important source of transcriptome and proteome complexity through selectively joining different coding elements to form mRNAs, which encode proteins with similar or distinct functions. In mammals, previous studies have shown the role of alternative splicing in regulating the function of the immune system, especially in the regulation of T-cell activation and function. As lower vertebrates, teleost fish mainly rely on a large family of pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) from various invading pathogens. In this review, we summarize recent advances in our understanding of alternative splicing of piscine PRRs including peptidoglycan recognition proteins (PGRPs), nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and their downstream signaling molecules, compared to splicing in mammals. We also discuss what is known and unknown about the function of splicing isoforms in the innate immune responses against pathogens infection in mammals and teleost fish. Finally, we highlight the consequences of alternative splicing in the innate immune system and give our view of important directions for future studies.
Highlights
In the initiation of innate immune responses against pathogens, pattern-recognition receptors (PRRs) have an essential role in recognizing the conserved pathogen-associated molecular patterns (PAMPs) and triggering immune responses to eliminate the invading microorganisms
We summarized what is known and unknown about the alternative splicing and the function of splicing isoforms from peptidoglycan recognition proteins (PGRPs), NLRs, RIG-I-like receptors (RLRs) and their downstream signaling molecules in response to pathogens infection in mammals and teleost fish
Significant advances have been achieved regarding the function of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and NOD2 in innate immune responses to bacterial, parasite and viral infections [51,52,53,54]
Summary
In the initiation of innate immune responses against pathogens, pattern-recognition receptors (PRRs) have an essential role in recognizing the conserved pathogen-associated molecular patterns (PAMPs) and triggering immune responses to eliminate the invading microorganisms. The most characteristic PRRs include Toll-like receptors (TLRs), peptidoglycan recognition proteins (PGRPs), Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) and RIG-I-like receptors (RLRs). The activation of these PRRs could initiate transcriptional and nontranscriptional innate immune responses, which tightly controlled signal transduction pathways and even directed the appropriate adaptive response [1,2,3]. We summarized what is known and unknown about the alternative splicing and the function of splicing isoforms from PGRPs, NLRs, RLRs and their downstream signaling molecules in response to pathogens infection in mammals and teleost fish. The other two NLRB and NLRP subfamilies were not identified in teleost fish, and NLRP may represent a mammalian expansion of NLR proteins [40]
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