Abstract
BackgroundThe mutation of insulin-like growth factor 2 (IGF2 mutation) that a single-nucleotide substitution (G→A) in the third intron of IGF2 abrogates the interaction with zinc finger BED-type containing 6 (ZBED6) and leads to increased muscle mass in pigs. IGF2 mutation knock-in (IGF2 KI) and ZBED6 knockout (ZBED6 KO) lead to changes in IGF2 expression and increase muscle mass in mice and pigs. Long noncoding RNAs (lncRNAs) may participate in numerous biological processes, including skeletal muscle development. However, the role of the ZBED6-lncRNA axis in skeletal muscle development is poorly characterized.ResultsIn this study, we assembled transcriptomes using RNA-seq data published in previous studies by our group and identified 11,408 known lncRNAs and 2269 potential lncRNAs in seven tissues, heart, longissimus dorsi, gastrocnemius muscle, liver, spleen, lung and kidney, of ZBED6 KO (lean mass model) and WT Bama pigs. ZBED6 affected the expression of 1570 lncRNAs (differentially expressed lncRNAs [DE-lncRNAs]; log2-fold change ≥ 1, nominal p-value ≤ 0.05) in the seven examined tissues. The expressed lncRNAs (FPKM > 0.1) exhibited tissue-specific patterns in WT pigs. Specifically, 3410 lncRNAs were expressed exclusively in only one tissue. Potential functions of lncRNAs were indirectly predicted by searching their target cis- and trans-regulated protein-coding genes. LncRNAs with tissue-specific expression influence numerous genes related to tissue functions. Weighted gene coexpression network analysis (WGCNA) of 1570 DE-lncRNAs between WT and ZBED6 KO pigs was used to define the following six lncRNA modules specific to different tissues: skeletal muscle, heart, lung, spleen, kidney and liver modules. Furthermore, by conjoint analysis of longissimus dorsi data (tissue-specific expression, muscle module and DE-lncRNAs) and ChIP-PCR revealed NONSUSG002145.1 (adjusted p-values = 0.044), which is coexpressed with the IGF2 gene and binding with ZBED6, may play important roles in ZBED6 KO pig skeletal muscle development.ConclusionsThese findings indicate that the identified lncRNAs may play essential roles in tissue function and regulate the mechanism of ZBED6 action in skeletal muscle development in pigs. To our knowledge, this is the first study describing lncRNAs in ZBED6 KO pigs. These results may open new research directions leading to a better understanding of the global functions of ZBED6 and of lncRNA functions in skeletal muscle development in pigs.
Highlights
The mutation of insulin-like growth factor 2 (IGF2 mutation) that a single-nucleotide substitution (G→A) in the third intron of IGF2 abrogates the interaction with zinc finger BED-type containing 6 (ZBED6) and leads to increased muscle mass in pigs
Wang et al BMC Genomics (2021) 22:593. These findings indicate that the identified Long non-coding RNA (lncRNA) may play essential roles in tissue function and regulate the mechanism of ZBED6 action in skeletal muscle development in pigs
Identification and characteristics of lncRNAs expressed in different tissues of WT and ZBED6 ZBED6 knockout (KO) pigs To comprehensively investigate the lncRNAs in WT and ZBED6 KO pigs, the Illumina HiSeq 2500 platform was used to obtain a comprehensive view of lncRNAs in seven tissues, namely, muscle, heart, liver, spleen, lung and kidney, between ZBED6 KO and WT pigs, with three biological replicates for each group
Summary
The mutation of insulin-like growth factor 2 (IGF2 mutation) that a single-nucleotide substitution (G→A) in the third intron of IGF2 abrogates the interaction with zinc finger BED-type containing 6 (ZBED6) and leads to increased muscle mass in pigs. In recent decades, increasing evidence has indicated that lncRNAs play important roles in many biological processes, such as the regulation of skeletal muscle development [5, 6], cell fate decisions [7], and subcutaneous fat deposition [8]. A single nucleotide transition from G to A in intron 3 of IGF2, a paternally expressed quantitative trait locus (QTL) in pigs, abrogates ZBED6-IGF2 binding and results in 3-fold greater postnatal expression of IGF2 mRNA in skeletal muscle, leading to increased muscle mass and heart size and reduced fat deposition in pigs. It is essential to elucidate the function of ZBED6 in pigs
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