Comprehensive analysis of pre-mRNA alternative splicing regulated by m6A methylation in pig oxidative and glycolytic skeletal muscles

Tan, Baohua; Zeng, Jiekang; Meng, Fanming; Wang, Shanshan; Xiao, Liyao; Zhao, Xinming; Hong, Linjun; Zheng, Enqin; Wu, Zhenfang; Li, Zicong; Gu, Tao

doi:10.1186/s12864-022-09043-0

Cited by 4 publications

(3 citation statements)

References 87 publications

(108 reference statements)

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“…The study found that the most abundant types of ASEs in all tissues were MEX and SE, consistent with other studies’ findings [ 26 , 27 ]. The common ASGs in the eight tissues accounted for 63.21–76.13% of each tissue, indicating a certain degree of conservation in the genes undergoing ASEs across tissues.…”

Section: Discussionsupporting

confidence: 92%

Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis through CCDC18

Liu,

Wang,

Liu

et al. 2024

IJMS

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Alternative splicing (AS) plays a crucial role in regulating gene expression, function, and diversity. However, limited reports exist on the identification and comparison of AS in Eastern and Western pigs. Here, we analyzed 243 transcriptome data from eight tissues, integrating information on transcription factors (TFs), selection signals, splicing factors (SFs), and quantitative trait loci (QTL) to comprehensively study alternative splicing events (ASEs) in pigs. Five ASE types were identified, with Mutually Exclusive Exon (MXE) and Skipped Exon (SE) ASEs being the most prevalent. A significant portion of genes with ASEs (ASGs) showed conservation across all eight tissues (63.21–76.13% per tissue). Differentially alternative splicing genes (DASGs) and differentially expressed genes (DEGs) exhibited tissue specificity, with blood and adipose tissues having more DASGs. Functional enrichment analysis revealed coDASG_DEGs in adipose were enriched in pathways associated with adipose deposition and immune inflammation, while coDASG_DEGs in blood were enriched in pathways related to immune inflammation and metabolism. Adipose deposition in Eastern pigs might be linked to the down-regulation of immune-inflammation-related pathways and reduced insulin resistance. The TFs, selection signals, and SFs appeared to regulate ASEs. Notably, ARID4A (TF), NSRP1 (SF), ANKRD12, IFT74, KIAA2026, CCDC18, NEXN, PPIG, and ROCK1 genes in adipose tissue showed potential regulatory effects on adipose-deposition traits. NSRP1 could promote adipogenesis by regulating alternative splicing and expression of CCDC18. Conducting an in-depth investigation into AS, this study has successfully identified key marker genes essential for pig genetic breeding and the enhancement of meat quality, which will play important roles in promoting the diversity of pork quality and meeting market demand.

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Section: Discussionsupporting

confidence: 92%

Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis through CCDC18

Liu,

Wang,

Liu

et al. 2024

IJMS

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“…In the present study, 40,052 selective shearing events corresponding to 9369 genes indicate that selective shearing genes are prevalent before and after adipocyte differentiation, with skipped exons being the most abundant type of selective shearing, similar to that reported in other livestock animals [15][16][17].…”

Section: Discussionsupporting

confidence: 85%

Comparative Genome-Wide Alternative Splicing Analysis between Preadipocytes and Adipocytes

Hou,

Li,

et al. 2024

Genes

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Alternative splicing is a ubiquitous regulatory mechanism in gene expression that allows a single gene to generate multiple messenger RNAs (mRNAs). Adipocyte development is regulated by many processes, and recent studies have found that splicing factors also play an important role in adipogenic development. In the present study, we further investigated the differences in selective shearing during different periods of adipocyte differentiation. We identified five alternative splicing types including skipped exon, mutually exclusive exon, Alternative 5′ splice site, Alternative 3′ splice site, and Retained intron, with skipped exons being the most abundant type of selective shearing. In total, 641 differentially expressed selective shearing genes were obtained, enriched in 279 pathways, from which we selected and verified the accuracy of the sequencing results. Overall, RNA-seq revealed changes in the splicing and expression levels of these new candidate genes between precursor adipocytes and adipocytes, suggesting that they may be involved in adipocyte generation and differentiation.

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“…Several studies report an association between m 6 A levels and alternative mRNA splicing [51,52] including the adenovirus transcriptome [53], although the underlying mechanisms were not elucidated. Long read sequencing identified the BCP-RNAs and we mapped two pC transcripts (pC-Long (L) or pC-Short (S)), pgRNA and a number of spliced RNAs which encode the 5' stem-loop DRACH motif (Fig 4D and S1 Table).…”

Section: Mapping the Hypoxic Hbv Transcriptome And Impact Of M 6 A Mo...mentioning

confidence: 99%

The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome

Tsukuda,

Harris,

Magri

et al. 2024

PLoS Pathog

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Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter (BCP). Here we show that the hypoxic-dependent increase in BCP-derived transcripts is dependent on N6-methyladenosine (m6A) modifications in the 5’ stem loop that regulate RNA half-life. Application of a probe-enriched long-read sequencing method to accurately map the HBV transcriptome showed an increased abundance of pre-genomic RNA under hypoxic conditions. Mapping the transcription start sites of BCP-RNAs identified a role for hypoxia to regulate pre-genomic RNA splicing that is dependent on m6A methylation. Bio-informatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region. In vitro studies with a human hepatocyte derived HepG2-NTCP cell line showed increased ALKBH5 gene expression under hypoxic conditions and a concomitant reduction in m6A-modified HBV BCP-RNA and host RNAs. Silencing the demethylase reduced the level of BCP-RNAs and host gene (CA9, NDRG1, VEGFA, BNIP3, FUT11, GAP and P4HA1) transcripts and this was mediated via reduced HIFα expression. In summary, our study highlights a previously unrecognized role for ALKBH5 in orchestrating viral and cellular transcriptional responses to low oxygen.

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Comprehensive analysis of pre-mRNA alternative splicing regulated by m6A methylation in pig oxidative and glycolytic skeletal muscles

Cited by 4 publications

References 87 publications

Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis through CCDC18

Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis through CCDC18

Comparative Genome-Wide Alternative Splicing Analysis between Preadipocytes and Adipocytes

The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome

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