scholarly journals Structural insights into the role of Dicer-related helicase 3 in RNAi in Caenorhabditis elegans.

2021 ◽  
Author(s):  
Kuohan Li ◽  
Jie Zheng ◽  
Melissa Wirawan ◽  
Trinh Mai Nguyen ◽  
Olga Fedorova ◽  
...  

DRH-3 belongs to the family of duplex RNA-dependent ATPases (DRAs), which include Dicer and RIG-I-like receptors (RLRs). DRH-3 is critically involved in germline development and RNAi-facilitated chromosome segregation via the 22G-siRNA pathway in C. elegans. The molecular understanding of DRH-3 and its function in endogenous RNAi pathways remains elusive. In this study, we solved the crystal structures of the DRH-3 N-terminal domain (NTD) and the C-terminal domains (CTDs) in complex with 5'-triphosphorylated RNAs. The NTD of DRH-3 adopts a distinct fold of tandem Caspase Activation and Recruitment Domains (CARDs) structurally similar to the CARDs of RIG-I and MDA5, suggesting a signaling function in the endogenous RNAi biogenesis. The CTD preferentially recognizes 5'-triphosphorylated double-stranded RNAs bearing the typical features of secondary siRNA transcripts. The full-length DRH-3 displays unique structural dynamics upon binding to RNA duplexes that differ from RIG-I or MDA5. These unique molecular features of DRH-3 help explain its function in RNAi in worms and the evolutionary divergence of the Dicer-like helicases.

2021 ◽  
Vol 12 ◽  
Author(s):  
Paulo G. Hofstatter ◽  
Gokilavani Thangavel ◽  
Marco Castellani ◽  
André Marques

Differently from the common monocentric organization of eukaryotic chromosomes, the so-called holocentric chromosomes present many centromeric regions along their length. This chromosomal organization can be found in animal and plant lineages, whose distribution suggests that it has evolved independently several times. Holocentric chromosomes present an advantage: even broken chromosome parts can be correctly segregated upon cell division. However, the evolution of holocentricity brought about consequences to nuclear processes and several adaptations are necessary to cope with this new organization. Centromeres of monocentric chromosomes are involved in a two-step cohesion release during meiosis. To deal with that holocentric lineages developed different adaptations, like the chromosome remodeling strategy in Caenorhabditis elegans or the inverted meiosis in plants. Furthermore, the frequency of recombination at or around centromeres is normally very low and the presence of centromeric regions throughout the entire length of the chromosomes could potentially pose a problem for recombination in holocentric organisms. However, meiotic recombination happens, with exceptions, in those lineages in spite of their holocentric organization suggesting that the role of centromere as recombination suppressor might be altered in these lineages. Most of the available information about adaptations to meiosis in holocentric organisms is derived from the animal model C. elegans. As holocentricity evolved independently in different lineages, adaptations observed in C. elegans probably do not apply to other lineages and very limited research is available for holocentric plants. Currently, we still lack a holocentric model for plants, but good candidates may be found among Cyperaceae, a large angiosperm family. Besides holocentricity, chiasmatic and achiasmatic inverted meiosis are found in the family. Here, we introduce the main concepts of meiotic constraints and adaptations with special focus in meiosis progression and recombination in holocentric plants. Finally, we present the main challenges and perspectives for future research in the field of chromosome biology and meiosis in holocentric plants.


2018 ◽  
Author(s):  
Dayana R D'Amora ◽  
Queenie Hu ◽  
Monica Pizzardi ◽  
Terrance Kubiseski

Background. Mutations in C. elegans can produce visible and quantifiable defects in morphology, lifespan, and development. BRAP2/IMP (BRCA1-associated binding protein 2) has been characterized as an E3 ubiquitin ligase, a general cytoplasmic retention factor, a potential scaffold protein, and is found to be widely expressed throughout various mammalian tissues, most highly in testes. However, its role in the development or health of these tissues has not been addressed. Results. The focus of this study is to determine the role of BRAP-2 in C. elegans germline development. We determined that brap-2 mutants display defects in germline morphology and a reduction in brood size. We also found that chromosomal abnormalities and embryonic lethality are elevated in brap-2 mutants following DNA damage, suggesting a potential role for BRAP-2 in facilitating DNA repair. Conclusions. Our findings indicate that BRAP-2 is required for C. elegans germline health and identifies a novel role for BRAP-2 in germline development.


2018 ◽  
Author(s):  
Dayana R D'Amora ◽  
Queenie Hu ◽  
Monica Pizzardi ◽  
Terrance Kubiseski

Background. Mutations in C. elegans can produce visible and quantifiable defects in morphology, lifespan, and development. BRAP2/IMP (BRCA1-associated binding protein 2) has been characterized as an E3 ubiquitin ligase, a general cytoplasmic retention factor, a potential scaffold protein, and is found to be widely expressed throughout various mammalian tissues, most highly in testes. However, its role in the development or health of these tissues has not been addressed. Results. The focus of this study is to determine the role of BRAP-2 in C. elegans germline development. We determined that brap-2 mutants display defects in germline morphology and a reduction in brood size. We also found that chromosomal abnormalities and embryonic lethality are elevated in brap-2 mutants following DNA damage, suggesting a potential role for BRAP-2 in facilitating DNA repair. Conclusions. Our findings indicate that BRAP-2 is required for C. elegans germline health and identifies a novel role for BRAP-2 in germline development.


2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.


2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.


1993 ◽  
Author(s):  
Michele Harway ◽  
◽  
Nancy Boyd-Franklin ◽  
Robert Geffner ◽  
Marsali Hansen ◽  
...  

2008 ◽  
Author(s):  
Ivelina Borisova ◽  
Theresa Betancourt ◽  
Wietse Tol ◽  
Ivan Komproe ◽  
Mark Jordans ◽  
...  
Keyword(s):  

2014 ◽  
Author(s):  
Merideth A. Robinson ◽  
Andrea C. Lewallen ◽  
Robyn Finckbone ◽  
Kristin Crocfer ◽  
Keith P. Klein ◽  
...  

2019 ◽  
Vol 11 (1) ◽  
pp. 51-56
Author(s):  
RIANI PRADARA JATI ◽  
Sekar Farah Nabila

  Penempatan peran yang baik bagi Family Caregiver sangatlah membantu lansia dalam meningkatkah qualitas hidupnya, meningkatkan motivasi dalam menjalankan hidup Penelitian ini bertujuan Mengetahui hubungan peran Family Caregiver dalam pemenuhan qualitas hidup bagi lansia di Kelurahan Langenharjo Kabupaten Kendal. DesainPenelitianDeskriptifKorelasional menggunakan pendekatan Krosectional,tehnikSamplingStratified Simple Random Sampling dengan karakteristik heterogen, dari populasi mempunyai hak yang sama untuk diseleksi sebagai sampel teknik undianPengambilan data dengan menggunakan kuesioner yang telah diuji validitas dan reliabilitasnya. Uji statistik Chi-square, dengan taraf signifikasi 5%jumlah sampel pada penelitian ini 70 sampel pada Family Caregiver dari 213 populasi yang ada. Hasil penelitian dari 70 responden didapatkan Peran Family Caregiver tidak baik dengan qualitas hidup tidak baik 33 (47,1%), sedangkan Peran Family Caregiver kurang baik dengan qualitas hidup lansia baik 3 (4,3%). Untuk distribusi Peran Family Caregiver kurang baik dengan qualitas hidup lansia tidak baik sebanyak 6 responden (8,6%) sedangkan untuk distribusi Peran Family Caregiver kurang baik dengan qualitas hidup lansia baik sebanyak 23 responden (32,9%). Terakhir, untuk distribusi Peran Family Caregiver baik dengan qualitas hidup lansia tidak baik didapatkan hasil 2 responden (2, 9%) sedangkan untuk distribusi Peran Family Caregiver baik dengan qualitas hidup lansia baik didapatkan hasil 3 responden (4,3%)Menunjukkan nilai ρ value 0,001 (ρ < 0,05) berarti ada hubungan antara dukungan keluarga dengan kepatuhan lansia dalam keikutsertaan posyandu lansia. Disarankan kepada semua Family Cregiver lansia untuk mampu memahami pentingnya perhatian, dukungan bagi lansia dalammeningkatkan qualitas hidup yang lebih baik bagi lansia.   Kata kunci : Peran family caregiver, qualitas hidup, lansia.   ABSTRACT Placement of a good role for Family Caregiver is very helpful for the elderly to improve their quality of life, increase motivation in living life Research Objective: To know the relationship between the role of Family Caregiver in fulfilling quality of life for the elderly in Langenharjo Village, Kendal Regency. Descriptive Correlational Research Design uses a cross sectional approach, Sampling Stratified Simple Random Sampling technique with heterogeneous characteristics, from the population has the same right to be selected as a sample lottery technique Retrieving data using a questionnaire that has been tested for validity and reliability. Test Chi-square statistics, with a significance level of 5% the number of samples in this study 70 samples on the Family Caregiver from 213 populations. Results of the Study Of 70 respondents found the role of Family Caregiver was not good with poor quality of life 33 (47.1%) , while the role of the Family Caregiver is not good with the quality of life of a good elderly 3 (4.3%). For the distribution of the role of Family Caregiver is not good with the quality of life of the poor family as many as 6 respondents (8.6%) while for the distribution of the Role of Family Caregiver is not good with the quality of life of good elderly as many as 23 respondents (32.9%). Finally, the distribution of the Role of Family Caregiver with good quality of life for the poor is obtained by 2 respondents (2, 9%), while the distribution of the Role of Family Caregiver with good quality of life for the elderly is obtained by 3 respondents (4.3%). 0.001 (ρ <0.05) means that there is a relationship between family support and the compliance of the elderly in the participation of the elderly posyandu. It is recommended to all elderly Cregiver families to be able to understand the importance of attention, support for the elderly in improving the quality of life better for the elderly   Keywords: Role of Family Caregiver, Quality of Life, Elderly


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