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  1. Article ; Online: Assessing the Role of 3D Vision Technology for Laparoscopy.

    Lai, Eric C H

    Annals of surgical oncology

    2022  Volume 29, Issue 11, Page(s) 6522–6523

    MeSH term(s) Humans ; Laparoscopy ; Operative Time ; Technology
    Language English
    Publishing date 2022-07-30
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1200469-8
    ISSN 1534-4681 ; 1068-9265
    ISSN (online) 1534-4681
    ISSN 1068-9265
    DOI 10.1245/s10434-022-11885-7
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  2. Article ; Online: Proliferation and dissemination of killer meiotic drive loci.

    Lai, Eric C / Vogan, Aaron A

    Current opinion in genetics & development

    2023  Volume 82, Page(s) 102100

    Abstract: Killer meiotic drive elements are selfish genetic entities that manipulate the sexual cycle to promote their own inheritance via destructive means. Two broad classes are sperm killers, typical of animals and plants, and spore killers, which are present ... ...

    Abstract Killer meiotic drive elements are selfish genetic entities that manipulate the sexual cycle to promote their own inheritance via destructive means. Two broad classes are sperm killers, typical of animals and plants, and spore killers, which are present in ascomycete fungi. Killer meiotic drive systems operate via toxins that destroy or disable meiotic products bearing the alternative allele. To avoid suicidal autotargeting, cells that bear these selfish elements must either lack the toxin target, or express an antidote. Historically, these systems were presumed to require large nonrecombining haplotypes to link multiple functional interacting loci. However, recent advances on fungal spore killers reveal that numerous systems are enacted by single genes, and similar molecular genetic studies in Drosophila pinpoint individual loci that distort gamete sex. Notably, many meiotic drivers duplicate readily, forming gene families that can have complex interactions within and between species, and providing substrates for their rapid functional diversification. Here, we summarize the known families of meiotic drivers in fungi and fruit flies, and highlight shared principles about their evolution and proliferation that promote the spread of these noxious genes.
    MeSH term(s) Male ; Animals ; Semen ; Alleles ; Drosophila/genetics ; Germ Cells ; Cell Proliferation
    Language English
    Publishing date 2023-08-23
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2023.102100
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  3. Article ; Online: Parameters of clustered suboptimal miRNA biogenesis.

    Shang, Renfu / Lai, Eric C

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 41, Page(s) e2306727120

    Abstract: The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon termed cluster assistance. Several features and biological impacts of this new layer of ... ...

    Abstract The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon termed cluster assistance. Several features and biological impacts of this new layer of miRNA regulation are not fully known. Here, we elucidate the parameters of cluster assistance of a suboptimal miRNA and also reveal competitive interactions amongst optimal miRNAs within a cluster. We exploit cluster assistance as a functional assay for suboptimal processing and use this to invalidate putative suboptimal substrates, as well as identify a "solo" suboptimal miRNA. Finally, we report complexity in how specific mutations might affect the biogenesis of clustered miRNAs in disease contexts. This includes how an operon context can buffer the effect of a deleterious processing variant, but reciprocally how a point mutation can have a nonautonomous effect to impair the biogenesis of a clustered, suboptimal, neighbor. These data expand our knowledge regarding regulated miRNA biogenesis in humans and represent a functional assay for empirical definition of suboptimal Microprocessor substrates.
    MeSH term(s) Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA Processing, Post-Transcriptional/genetics ; RNA-Binding Proteins/metabolism ; Ribonuclease III/genetics ; Ribonuclease III/metabolism
    Chemical Substances MicroRNAs ; RNA-Binding Proteins ; Ribonuclease III (EC 3.1.26.3)
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2306727120
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  4. Article: Regulation of the Alternative Neural Transcriptome by ELAV/Hu RNA Binding Proteins.

    Wei, Lu / Lai, Eric C

    Frontiers in genetics

    2022  Volume 13, Page(s) 848626

    Abstract: The process of alternative polyadenylation (APA) generates multiple 3' UTR isoforms for a given locus, which can alter regulatory capacity and on occasion change coding potential. APA was initially characterized for a few genes, but in the past decade, ... ...

    Abstract The process of alternative polyadenylation (APA) generates multiple 3' UTR isoforms for a given locus, which can alter regulatory capacity and on occasion change coding potential. APA was initially characterized for a few genes, but in the past decade, has been found to be the rule for metazoan genes. While numerous differences in APA profiles have been catalogued across genetic conditions, perturbations, and diseases, our knowledge of APA mechanisms and biology is far from complete. In this review, we highlight recent findings regarding the role of the conserved ELAV/Hu family of RNA binding proteins (RBPs) in generating the broad landscape of lengthened 3' UTRs that is characteristic of neurons. We relate this to their established roles in alternative splicing, and summarize ongoing directions that will further elucidate the molecular strategies for neural APA, the
    Language English
    Publishing date 2022-02-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2022.848626
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  5. Article ; Online: Social determinants of intrinsic capacity: A systematic review of observational studies.

    Huang, Zi-Ting / Lai, Eric T C / Luo, Yan / Woo, Jean

    Ageing research reviews

    2024  Volume 95, Page(s) 102239

    Abstract: Background: The World Health Organization defined healthy ageing as the maintenance of functional ability with ageing. Intrinsic capacity is a measurement of healthy ageing, and can be shaped by social determinants. However, an overall understanding of ... ...

    Abstract Background: The World Health Organization defined healthy ageing as the maintenance of functional ability with ageing. Intrinsic capacity is a measurement of healthy ageing, and can be shaped by social determinants. However, an overall understanding of how multiple social determinants contribute to intrinsic capacity remains unclear. We aim to summarize observational studies investigating the relationships between social determinants and intrinsic capacity among community-dwelling adults.
    Methods: A systematic search was conducted through Medline, Embase, PsycInfo, Web of Science, and CINAHL until August 14, 2023.
    Results: After reviewing 813 articles, we included 21 studies from nine countries in Asia, Europe, and America. Seventeen studies used a cross-sectional design and the others were longitudinal studies. Social determinants related to intrinsic capacity can be classified into five domains, containing socioeconomic status (16, 76.2% of studies), lifestyles (14, 66.7%), psychosocial factors (9, 42.9%), material circumstances (4, 19.0%), and healthcare systems (1, 4.8%). Strong evidence supported that better intrinsic capacity was associated with higher education, higher wealth, more physical activities, no smoking, more social engagement, and being married or partnered. The relationships of intrinsic capacity with dietary patterns and alcohol drinking were contradictory across studies. Research on the associations of working status, housing environments, and healthcare accessibility with intrinsic capacity was insufficient to draw conclusions.
    Conclusion: These findings highlight roles of socioeconomic status, lifestyles, and psychosocial factors in improving intrinsic capacity thus promoting healthy ageing. Future research is needed to investigate causal relationships between social determinants and intrinsic capacity, especially material circumstances and healthcare systems.
    MeSH term(s) Humans ; Aging ; Europe ; Social Determinants of Health ; Observational Studies as Topic
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article ; Systematic Review
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2024.102239
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    Zs.A 5579: Show issues Location:
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  6. Article ; Online: Regulation of alternative splicing and polyadenylation in neurons.

    Lee, Seungjae / Aubee, Joseph I / Lai, Eric C

    Life science alliance

    2023  Volume 6, Issue 12

    Abstract: Cell-type-specific gene expression is a fundamental feature of multicellular organisms and is achieved by combinations of regulatory strategies. Although cell-restricted transcription is perhaps the most widely studied mechanism, co-transcriptional and ... ...

    Abstract Cell-type-specific gene expression is a fundamental feature of multicellular organisms and is achieved by combinations of regulatory strategies. Although cell-restricted transcription is perhaps the most widely studied mechanism, co-transcriptional and post-transcriptional processes are also central to the spatiotemporal control of gene functions. One general category of expression control involves the generation of multiple transcript isoforms from an individual gene, whose balance and cell specificity are frequently tightly regulated via diverse strategies. The nervous system makes particularly extensive use of cell-specific isoforms, specializing the neural function of genes that are expressed more broadly. Here, we review regulatory strategies and RNA-binding proteins that direct neural-specific isoform processing. These include various classes of alternative splicing and alternative polyadenylation events, both of which broadly diversify the neural transcriptome. Importantly, global alterations of splicing and alternative polyadenylation are characteristic of many neural pathologies, and recent genetic studies demonstrate how misregulation of individual neural isoforms can directly cause mutant phenotypes.
    MeSH term(s) Polyadenylation/genetics ; Alternative Splicing/genetics ; RNA Splicing ; Protein Isoforms/genetics ; Neurons
    Chemical Substances Protein Isoforms
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202302000
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  7. Article ; Online: A comprehensive dataset of microRNA misexpression phenotypes in the

    Bejarano, Fernando / Lai, Eric C

    Data in brief

    2021  Volume 36, Page(s) 107037

    Abstract: microRNAs (miRNAs) are a broad class of ~22 nucleotide regulatory RNA, which collectively have broad effects on the transcriptome and are involved in diverse biology, from development and adult physiology, and from homeostasis to disease and pathology. ... ...

    Abstract microRNAs (miRNAs) are a broad class of ~22 nucleotide regulatory RNA, which collectively have broad effects on the transcriptome and are involved in diverse biology, from development and adult physiology, and from homeostasis to disease and pathology. We investigated the effects of systematically expressing microRNAs (miRNAs) during the development of the
    Language English
    Publishing date 2021-04-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2021.107037
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  8. Article ; Online: The determinants of longevity: The perspectives from East Asian economies.

    Lai, Eric T C / Chiang, Tung-Liang / Kim, Chang-Yup / Hashimoto, Hideki / Marmot, Michael / Woo, Jean

    Journal of the American Geriatrics Society

    2023  Volume 71, Issue 10, Page(s) 3338–3341

    MeSH term(s) Humans ; East Asian People/statistics & numerical data ; Longevity ; Asia, Eastern/epidemiology
    Language English
    Publishing date 2023-05-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80363-7
    ISSN 1532-5415 ; 0002-8614
    ISSN (online) 1532-5415
    ISSN 0002-8614
    DOI 10.1111/jgs.18418
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  9. Article ; Online: microRNAs in action: biogenesis, function and regulation.

    Shang, Renfu / Lee, Seungjae / Senavirathne, Gayan / Lai, Eric C

    Nature reviews. Genetics

    2023  Volume 24, Issue 12, Page(s) 816–833

    Abstract: Ever since microRNAs (miRNAs) were first recognized as an extensive gene family >20 years ago, a broad community of researchers was drawn to investigate the universe of small regulatory RNAs. Although core features of miRNA biogenesis and function were ... ...

    Abstract Ever since microRNAs (miRNAs) were first recognized as an extensive gene family >20 years ago, a broad community of researchers was drawn to investigate the universe of small regulatory RNAs. Although core features of miRNA biogenesis and function were revealed early on, recent years continue to uncover fundamental information on the structural and molecular dynamics of core miRNA machinery, how miRNA substrates and targets are selected from the transcriptome, new avenues for multilevel regulation of miRNA biogenesis and mechanisms for miRNA turnover. Many of these latest insights were enabled by recent technological advances, including massively parallel assays, cryogenic electron microscopy, single-molecule imaging and CRISPR-Cas9 screening. Here, we summarize the current understanding of miRNA biogenesis, function and regulation, and outline challenges to address in the future.
    MeSH term(s) MicroRNAs/genetics ; Transcriptome
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2023-06-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/s41576-023-00611-y
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  10. Article ; Online: The Exon Junction Complex and intron removal prevent re-splicing of mRNA.

    Joseph, Brian / Lai, Eric C

    PLoS genetics

    2021  Volume 17, Issue 5, Page(s) e1009563

    Abstract: Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the ... ...

    Abstract Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic SS, even though most bear weak splicing motifs and are seemingly incompetent. Mechanistically, the EJC directly conceals cryptic splicing elements by virtue of its position-specific recruitment, preventing aberrant SS definition. Unexpectedly, we discover the EJC inhibits scores of regenerated 5' and 3' recursive SS on segments that have already undergone splicing, and that loss of EJC regulation triggers faulty resplicing of mRNA. An important corollary is that certain intronless cDNA constructs yield unanticipated, truncated transcripts generated by resplicing. We conclude the EJC has conserved roles to defend transcriptome fidelity by (1) repressing illegitimate splice sites on pre-mRNAs, and (2) preventing inadvertent activation of such sites on spliced segments.
    MeSH term(s) Alternative Splicing ; Animals ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Exons/genetics ; Introns/genetics ; Multiprotein Complexes ; RNA Splice Sites/genetics ; RNA Splicing ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome
    Chemical Substances Multiprotein Complexes ; RNA Splice Sites ; RNA, Messenger
    Language English
    Publishing date 2021-05-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009563
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