• Genomics & Informatics
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• v.21 no.1
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• pp.2.1-2.14
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• 2023

Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

• Animal Bioscience
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• v.35 no.10
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• pp.1512-1523
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• 2022

Objective: The growth of pigs involves multiple regulatory mechanisms, and modern molecular breeding techniques can be used to understand the skeletal muscle growth and development to promote the selection process of pigs. This study aims to explore candidate lncRNAs and mRNAs related to skeletal muscle growth and development among Duroc pigs with different average daily gain (ADG). Methods: A total of 8 pigs were selected and divided into two groups: H group (high-ADG) and L group (low-ADG). And followed by whole transcriptome sequencing to identify differentially expressed (DE) lncRNAs and mRNAs. Results: In RNA-seq, 703 DE mRNAs (263 up-regulated and 440 down-regulated) and 74 DE lncRNAs (45 up-regulated and 29 down-regulated) were identified. In addition, 1,418 Transcription factors (TFs) were found. Compared with mRNAs, lncRNAs had fewer exons, shorter transcript length and open reading frame length. DE mRNAs and DE lncRNAs can form 417 lncRNA-mRNA pairs (antisense, cis and trans). DE mRNAs and target genes of lncRNAs were enriched in cellular processes, biological regulation, and regulation of biological processes. In addition, quantitative trait locus (QTL) analysis was used to detect the functions of DE mRNAs and lncRNAs, the most of DE mRNAs and target genes of lncRNAs were enriched in QTLs related to growth traits and skeletal muscle development. In single-nucleotide polymorphism/insertion-deletion (SNP/INDEL) analysis, 1,081,182 SNP and 131,721 INDEL were found, and transition was more than transversion. Over 60% of percentage were skipped exon events among alternative splicing events. Conclusion: The results showed that different ADG among Duroc pigs with the same diet maybe due to the DE mRNAs and DE lncRNAs related to skeletal muscle growth and development.

• BMB Reports
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• v.43 no.5
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• pp.344-348
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• 2010

Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Staufen2 is an mRNA-binding protein expressed in the cell bodies and cellular processes of different brain cells. It is notably involved in the transport of dendritic mRNAs along microtubules. Its knockdown expression was shown to change spine morphology and impair synaptic functions. However, the identity of Staufen2-bound mRNAs in brain cells is still completely unknown. As a mean to identify these mRNAs, we immunoprecipitated Staufen2-containing mRNPs from embryonic rat brains and used a genome wide approach to identify Staufen2-associated mRNAs. The genome wide approach identified 1780 mRNAs in Staufen2-containing mRNPs that code for proteins involved in cellular processes such as post-translational protein modifications, RNA metabolism, intracellular transport and translation. These results represent an additional and important step in the characterization of Staufen2- mediated neuronal functions in rat brains.

• Molecules and Cells
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• v.37 no.1
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• pp.1-8
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• 2014

Mammalian-cell messenger RNAs (mRNAs) are generated in the nucleus from precursor RNAs (pre-mRNAs, which often contain one or more introns) that are complexed with an array of incompletely inventoried proteins. During their biogenesis, pre-mRNAs and their derivative mRNAs are subject to extensive cis-modifications. These modifications promote the binding of distinct polypeptides that mediate a diverse array of functions needed for mRNA metabolism, including nuclear export, inspection by the nonsense-mediated mRNA decay (NMD) quality-control machinery, and synthesis of the encoded protein product. Ribonucleoprotein complex (RNP) remodeling through the loss and gain of protein constituents before and after pre-mRNA splicing, during mRNA export, and within the cytoplasm facilitates NMD, ensuring integrity of the transcriptome. Here we review the mRNP rearrangements that culminate in detection and elimination of faulty transcripts by mammalian-cell NMD.

• Molecules and Cells
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• v.38 no.10
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• pp.895-903
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• 2015

Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.

• Molecules and Cells
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• v.37 no.5
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• pp.412-417
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• 2014

It has been reported that exogenously introduced micro-RNA (exo-miRNA) competes with endogenously expressed miRNAs (endo-miRNAs) in human cells, resulting in a detectable upregulation of mRNAs with endo-miRNA target sites (TSs). However, the detailed mechanisms of the competition between exo- and endo-miRNAs remain uninvestigated. In this study, using 74 microarrays that monitored the whole-transcriptome response after introducing miRNAs or siRNAs into HeLa cells, we systematically examined the derepression of mRNAs with exo- and/or endo-miRNA TSs. We quantitatively assessed the effect of the number of endo-miRNA TSs on the degree of mRNA derepression. As a result, we observed that the number of endo-miRNA TSs was significantly associated with the degree of derepression, supporting that the derepression resulted from the competition between exo- and endo-miRNAs. However, when we examined whether the site proficiency of exo-miRNA TSs could also influence mRNA derepression, to our surprise, we discovered a strong positive correlation. Our analysis indicates that site proficiencies of both exo- and endo-miRNA TSs are important determinants for the degree of mRNA derepression, implying that the derepression of mRNAs in response to exo-miRNA is more complex than that currently perceived. Our observations may lead to a more complete understanding of the detailed mechanisms of the competition between exo- and endo-miRNAs and to a more accurate prediction of miRNA targets. Our analysis also suggests an interesting hypothesis that long 3'-UTRs may function as molecular buffer against gene expression regulation by individual miRNAs.

• Genomics & Informatics
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• v.14 no.3
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• pp.112-124
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• 2016

Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs). Argonaute (AGO) protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism. In the current work, 64 genes and 23 miRNAs have been selected from literatures, whose deregulation is well established in seven types of solid cancer like lung, breast, prostate, pancreases, colorectal, stomach, and bladder cancer. In silico study reveals, miRNAs namely, miR-106a, miR-21, and miR-29b-2 have a strong binding affinity towards PTEN, TGFBR2, and VEGFA genes, respectively, suggested as important factors in RNA silencing mechanism. Furthermore, interaction between AGO protein (PDB ID-3F73, chain A) with selected miRNAs and with miRNAs-mRNAs duplex were studied computationally to understand their binding at molecular level. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding miRNAs based gene silencing mechanism in solid cancer.

• Plant Biotechnology Reports
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• v.3 no.2
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• pp.111-126
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• 2009

MicroRNAs (miRNAs) are endogenous, non-coding, small RNA molecules consisting of 21-24 nucleotides (nts) that regulate target genes at the posttranscriptional level in plants and animals. In plants, miRNAs negatively regulate target mRNAs containing a highly complementary sequence by either mRNA cleavage or translational repression. MiRNAs are processed from single-stranded precursors containing stem-loop structures by a Dicer-like enzyme and are loaded into silencing complexes, where they act on target mRNAs. Although plant miRNAs were first reported in Arabidopsis 10 years later than animal miRNAs, numerous miRNAs have since been identified from various land plants ranging from mosses to flowering plants, and their roles in diverse aspects of plant developmental processes have been characterized. Furthermore, most of the annotated plant miRNAs are evolutionarily conserved in various plants. In particular, recent functional studies using Arabidopsis mutants have contributed a great deal of information towards establishing a framework for understanding miRNA biogenesis and functional roles. Extensive appraisal of miRNA-directed regulation during a wide array of plant development and plant responses to environmental conditions has confirmed the versatile roles of miRNAs as a key component of plant molecular biology.

• Genomics & Informatics
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• v.13 no.2
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• pp.45-52
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• 2015

Acute myeloid leukemia is a well characterized blood cancer in which the unnatural growth of immature white blood cell takes place, where several genes transcription is regulated by the micro RNAs (miRNAs). Argonaute (AGO) protein is a protein family that binds to the miRNAs and mRNA complex where a strong binding affinity is crucial for its RNA silencing function. By understanding pattern recognition between the miRNAs-mRNA complex and its binding affinity with AGO protein, one can decipher the regulation of a particular gene and develop suitable siRNA for the same in disease condition. In the current work, HOXA9 gene has been selected from literature, whose deregulation is well-established in acute myeloid leukemia. Four miRNAs (mir-145, mir-126, let-7a, and mir-196b) have been selected to target mRNA of HOXA9 (NCBI accession No. NM_152739.3). The binding interaction between mRNAs and mRNA of HOXA9 gene was studied computationally. From result, it was observed mir-145 has highest affinity for HOXA9 gene. Furthermore, the interaction between miRNAs-mRNA duplex of all chosen miRNAs are docked with AGO protein (PDB ID: 3F73, chain A) to study their interaction at molecular level through an in silico approach. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding of AGO-assisted miRNA based gene silencing mechanism in HOXA9 gene associated in acute myeloid leukemia computationally.

• Animal Bioscience
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• v.35 no.1
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• pp.115-125
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• 2022

Objective: Intramuscular fat (IMF) is a critical economic indicator of pork quality. Studies on IMF among different pig breeds have been performed via high-throughput sequencing, but comparisons within the same pig breed remain unreported. Methods: This study was performed to explore the gene profile and identify candidate long noncoding RNA (lncRNAs) and mRNAs associated with IMF deposition among Laiwu pigs with different IMF contents. Based on the longissimus dorsi muscle IMF content, eight pigs from the same breed and management were selected and divided into two groups: a high IMF (>12%, H) and low IMF group (<5%, L). Whole-transcriptome sequencing was performed to explore the differentially expressed (DE) genes between these two groups. Results: The IMF content varied greatly among Laiwu pig individuals (2.17% to 13.93%). Seventeen DE lncRNAs (11 upregulated and 6 downregulated) and 180 mRNAs (112 upregulated and 68 downregulated) were found. Gene Ontology analysis indicated that the following biological processes played an important role in IMF deposition: fatty acid and lipid biosynthetic processes; the extracellular signal-regulated kinase cascade; and white fat cell differentiation. In addition, the peroxisome proliferator-activated receptor, phosphatidylinositol-3-kinase-protein kinase B, and mammalian target of rapamycin pathways were enriched in the pathway analysis. Intersection analysis of the target genes of DE lncRNAs and mRNAs revealed seven candidate genes associated with IMF accumulation. Five DE lncRNAs and 20 DE mRNAs based on the pig quantitative trait locus database were identified and shown to be related to fat deposition. The expression of five DE lncRNAs and mRNAs was verified by quantitative real time polymerase chain reaction (qRT-PCR). The results of qRT-PCR and RNA-sequencing were consistent. Conclusion: These results demonstrated that the different IMF contents among pig individuals may be due to the DE lncRNAs and mRNAs associated with lipid droplets and fat deposition.