1.Advances of enhancers in regulating craniomaxillofacial development in mammals.
Hao LIU ; Jie Wen DAI ; Gang DING
Chinese Journal of Stomatology 2022;57(9):978-982
As a key regulatory element of gene differential expression, enhancer plays a crucial role in craniomaxillofacial development through regulating the spatiotemporal expression of target genes to promote tissue-specific differentiation. With the development of CRISPR and chromosome conformation capture technique, the function of enhancer and its regulatory mechanism has been explored in depth. This paper gave a systematic review on the mechanism of enhancer regulating target gene expression and the role of enhancer in oral craniofacial development and malformation.
Animals
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Enhancer Elements, Genetic
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Mammals/genetics*
2.Co-regulation of circadian clock genes and microRNAs in bone metabolism.
Tingting LI ; Shihua ZHANG ; Yuxuan YANG ; Lingli ZHANG ; Yu YUAN ; Jun ZOU
Journal of Zhejiang University. Science. B 2022;23(7):529-546
Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.
Animals
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Circadian Clocks/genetics*
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Circadian Rhythm/genetics*
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Mammals/genetics*
;
MicroRNAs/genetics*
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Osteogenesis/genetics*
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Osteoporosis/genetics*
3.Specialized gene expression and regulation in the epididymis.
National Journal of Andrology 2006;12(1):71-74
The epididymis is a single and highly convoluted tubule system in mammals. The epithelium is the major compartment for epididymal function. Proteins synthesized and secreted by epididymal epithelium provide a special and ever-changing luminal fluid environment for sperm as they progress through the epididymis, which makes sperm achieve motility and ultimately results in sperm functional maturation. Specialized genes expressed in the epididymis have regional-specific characteristics. They are regulated by androgen and/or testicular factors and present spatial and tempel-specialized expression pattern in postnatal development, all these hint that they play important and unique roles in epididymis.
Animals
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Epididymal Secretory Proteins
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genetics
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Epididymis
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physiology
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Gene Expression Regulation, Developmental
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Male
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Mammals
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Sperm Maturation
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genetics
4.Pathways and mechanisms of RNA interference mediated by viral siRNA.
Chinese Journal of Biotechnology 2021;37(4):1237-1248
RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the antiviral strategy of host. Early studies reveal that invertebrates can use RNAi to resist viruses. However, if this mechanism exists in mammals is still controversial. The latest studies confirm that mammals do have the RNAi-based immunity, and researchers believe that RNAi-based antiviral immunity is a brand-new immunological mechanism that was neglected in the past. It is worthy to note that virus can also use RNAi to enhance its infectivity and immune escape in host cells. This review introduces the research history of RNAi-based antiviral immunity in animals and summarizes the main findings in this field. Last but not least, we indicate a series of unresolved questions about RNAi-based antiviral immunity, and explore the relationship between RNAi-based antiviral immunity and other innate immunological pathways. The virus-mediated RNAi pathway in animal is not only an interesting basic biology question, but also has important guiding roles in the development of antiviral drugs.
Animals
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Antiviral Agents
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Immunity, Innate/genetics*
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Mammals
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RNA Interference
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RNA, Small Interfering/genetics*
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RNA, Viral
5.Homology-based repair induced by CRISPR-Cas nucleases in mammalian embryo genome editing.
Xiya ZHANG ; Tao LI ; Jianping OU ; Junjiu HUANG ; Puping LIANG
Protein & Cell 2022;13(5):316-335
Recent advances in genome editing, especially CRISPR-Cas nucleases, have revolutionized both laboratory research and clinical therapeutics. CRISPR-Cas nucleases, together with the DNA damage repair pathway in cells, enable both genetic diversification by classical non-homologous end joining (c-NHEJ) and precise genome modification by homology-based repair (HBR). Genome editing in zygotes is a convenient way to edit the germline, paving the way for animal disease model generation, as well as human embryo genome editing therapy for some life-threatening and incurable diseases. HBR efficiency is highly dependent on the DNA donor that is utilized as a repair template. Here, we review recent progress in improving CRISPR-Cas nuclease-induced HBR in mammalian embryos by designing a suitable DNA donor. Moreover, we want to provide a guide for producing animal disease models and correcting genetic mutations through CRISPR-Cas nuclease-induced HBR in mammalian embryos. Finally, we discuss recent developments in precise genome-modification technology based on the CRISPR-Cas system.
Animals
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CRISPR-Cas Systems/genetics*
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DNA/genetics*
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Embryo, Mammalian/metabolism*
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Endonucleases/metabolism*
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Gene Editing
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Mammals/metabolism*
6.Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases.
Xin YIN ; Azhar ANWAR ; Yanbo WANG ; Huanhuan HU ; Gaoli LIANG ; Chenyu ZHANG
Frontiers of Medicine 2022;16(2):176-184
Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.
Animals
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Environmental Exposure
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Epigenesis, Genetic
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Female
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Humans
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Male
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Mammals/genetics*
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Pregnancy
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RNA, Small Untranslated/genetics*
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Spermatozoa
7.Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions.
Mengyuan LYU ; Hongli LAI ; Yili WANG ; Yanbing ZHOU ; Yi CHEN ; Dongsheng WU ; Jie CHEN ; Binwu YING
Chinese Medical Journal 2023;136(7):767-779
Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.
Animals
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Alternative Splicing/genetics*
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RNA Splicing
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Spliceosomes/metabolism*
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RNA, Messenger/metabolism*
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Communicable Diseases/genetics*
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Mammals/metabolism*
8.Mammalian DMRTs: Structure, function and relationship with cancer.
Hai-Long LI ; Zi-Cong ZOU ; Chi FANG ; Yi-Ping ZHENG ; Xiao-Ming GUO ; Wei-Hong YANG
Acta Physiologica Sinica 2023;75(2):269-278
DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.
Male
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Animals
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Humans
;
Mice
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Transcription Factors/genetics*
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Mammals/metabolism*
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Cell Differentiation
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Neoplasms/genetics*
9.Analysis of the structure of chicken Foxp3 and its expression profile in tissues.
He CHANG ; Hui GAO ; Yongqiang WANG ; Li GAO ; Hong CAO ; Xiaoqi LI ; Shijun ZHENG
Chinese Journal of Biotechnology 2022;38(8):2928-2938
In this study, we cloned the complete coding sequence (CDS) of chicken foxp3 (chfoxp3) gene, analyzed its structure, and investigated its expression profile in different chicken tissues. To be specific, chfoxp3 was cloned from the splenic tissue of 50-day-old specific-pathogen-free chickens, and analyzed by using online bioinformatics tools or software. The expression profiles of the chfoxp3 gene in different chicken tissues were detected by quantitative real-time PCR (qRT-PCR). The results indicated that the chfoxp3 gene contains an 882-bp open reading frame, encoding 293 amino acids hydrophilic protein with a molecular weight of 33.44 kDa. The chFoxp3 protein has a forkhead domain and carries a nuclear localization signal, which is typical in the Fox transcription factor family. The secondary structure of chFoxp3 consists of α-helix (29.35%), extended chain (10.92%), β-turn (5.12%) and random coil (54.61%). The expression of chfoxp3 varied in different tissues. The expression levels of chfoxp3 in chicken heart and pancreas were higher than in spleen, bursa of Fabricius, thymus, and other immune organs (P < 0.01), which was quite different from that of mammals. Phylogenetic tree analysis showed that chFoxp3 belonged to the same clade as other wild birds did, but was far different from that of mammals. These results may facilitate further research on the role of chFoxp3 in immune regulation.
Amino Acid Sequence
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Animals
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Chickens/genetics*
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Cloning, Molecular
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Gene Expression Regulation
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Mammals/genetics*
;
Phylogeny
10.Single chain antibody fragment display systems: a review.
Yao CHEN ; Xingfu SHU ; Yu ZHAO ; Bowen ZHANG ; Zhongren MA ; Haixia ZHANG
Chinese Journal of Biotechnology 2023;39(9):3681-3694
Single chain antibody fragment (scFv) is a small molecule composed of a variable region of heavy chain (VH) and a variable region of light chain (VL) of an antibody, and these two chains are connected by a flexible short peptide. scFv is the smallest functional fragment with complete antigen-binding activity, which contains both the antibody-recognizing site and the antigen-binding site. Compared with other antibodies, scFv has the advantages of small molecular weight, strong penetration, low immunogenicity, and easy expression. Currently, the most commonly used display systems for scFv mainly include the phage display system, ribosome display system, mRNA display system, yeast cell surface display system and mammalian cell display system. In recent years, with the development of scFv in the field of medicine, biology, and food safety, they have also attracted much attention in the sectors of biosynthesis and applied research. This review summarizes the advances of scFv display systems in recent years in order to facilitate scFv screening and application.
Animals
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Immunoglobulin Variable Region/genetics*
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Immunoglobulin Fragments/metabolism*
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Single-Chain Antibodies/metabolism*
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Peptide Library
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Mammals/genetics*