Functions and applications of RNA interference and small regulatory RNAs.

Small regulatory RNAs play a variety of crucial roles in eukaryotes, influencing gene regulation, developmental timing, antiviral defense, and genome integrity via a process termed RNA interference (RNAi). This process involves Argonaute/small RNA (AGO/sRNA) complexes that target transcripts via sequence complementarity and modulate gene expression and epigenetic modifications. RNAi is a highly conserved gene regulatory phenomenon that recognizes self- and non-self nucleic acids, thereby defending against invasive sequences.

Nucleolar stress induces nucleolar stress body formation via the NOSR-1/NUMR-1 axis in Caenorhabditis elegans.

Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identify a subnuclear organelle named the nucleolar stress body (NoSB), the formation of which is induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C.

Germ granule compartments coordinate specialized small RNA production.

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C.

ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.

Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (HO), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens in to identify a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles.

The absence of the ribosomal protein Rpl2702 elicits the MAPK-mTOR signaling to modulate mitochondrial morphology and functions.

Ribosomes mediate protein synthesis, which is one of the most energy-demanding activities within the cell, and mitochondria are one of the main sources generating energy. How mitochondrial morphology and functions are adjusted to cope with ribosomal defects, which can impair protein synthesis and affect cell viability, is poorly understood. Here, we used the fission yeast Schizosaccharomyces Pombe as a model organism to investigate the interplay between ribosome and mitochondria.

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates , a gene encoding the conserved transmembrane tetraspanin in .

xQTLbiolinks: a comprehensive and scalable tool for integrative analysis of molecular QTLs.

Genome-wide association studies (GWAS) have identified thousands of disease-associated non-coding variants, posing urgent needs for functional interpretation. Molecular Quantitative Trait Loci (xQTLs) such as eQTLs serve as an essential intermediate link between these non-coding variants and disease phenotypes and have been widely used to discover disease-risk genes from many population-scale studies. However, mining and analyzing the xQTLs data presents several significant bioinformatics challenges, particularly when it comes to integration with GWAS data.

Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer.

Natural selection drives the acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisitions in immunity, metabolic, and reproduction function via interdomain HGT (iHGT) from bacteria. Here, we report that the nematode gene rml-3 has been acquired by iHGT from bacteria and that it enables exoskeleton resilience and protection against environmental toxins in Caenorhabditis elegans.

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here we show that early-life thermal stress strongly up-regulates , a gene encoding the conserved transmembrane tetraspanin in .

rRNA intermediates coordinate the formation of nucleolar vacuoles in C. elegans.

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C.

Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans.

The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases.

A ZTF-7/RPS-2 complex mediates the cold-warm response in C. elegans.

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm.

H3K9me1/2 methylation limits the lifespan of mutants in .

Histone methylation plays crucial roles in the development, gene regulation, and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of putative histone 3 lysine 9 mono/dimethyltransferase genes ( and ), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (insulin growth factor 1 [IGF-1] receptor) mutant in .

ipaQTL-atlas: an atlas of intronic polyadenylation quantitative trait loci across human tissues.

Functional interpretation of disease-associated non-coding variants remains a significant challenge in the post-GWAS era. Our recent study has identified 3'UTR alternative polyadenylation (APA) quantitative trait loci (3'aQTLs) and connects APA events with QTLs as a major driver of human traits and diseases. Besides 3'UTR, APA events can also occur in intron regions, and increasing evidence has connected intronic polyadenylation with disease risk.

The SNAPc complex mediates starvation-induced trans-splicing in Caenorhabditis elegans.

Dietary restriction usually suppresses biosynthesis but activates catabolic pathways in animals. However, the short-term starvation enhances biosynthetic activities and promotes ribosomal biogenesis in adult Caenorhabditis elegans. The mechanism underlying the processes remains largely unknown.

Molecular basis for PICS-mediated piRNA biogenesis and cell division.

By incorporating two mutually exclusive factors, PID-1 and TOST-1, C. elegans PICS complex plays important roles in piRNA biogenesis, chromosome segregation and cell division. We firstly map the interaction network between PICS subunits, then uncover the mechanisms underlying the interactions between PICS subunits by solving several complex structures, including those of TOFU-6/PICS-1, ERH-2/PICS-1, and ERH-2/TOST-1.

Structural recognition of the mRNA 3' UTR by PUF-8 restricts the lifespan of C. elegans.

The molecular mechanisms of aging are unsolved fundamental biological questions. Caenorhabditis elegans is an ideal model organism for investigating aging. PUF-8, a PUF (Pumilio and FBF) protein in C.

Antisense ribosomal siRNAs inhibit RNA polymerase I-directed transcription in C. elegans.

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans.

A chromodomain protein mediates heterochromatin-directed piRNA expression.

PIWI-interacting RNAs (piRNAs) play significant roles in suppressing transposons, maintaining genome integrity, and defending against viral infections. How piRNA source loci are efficiently transcribed is poorly understood. Here, we show that in , transcription of piRNA clusters depends on the chromatin microenvironment and a chromodomain-containing protein, UAD-2.

Functional Proteomics Identifies a PICS Complex Required for piRNA Maturation and Chromosome Segregation.

piRNAs play significant roles in suppressing transposons and nonself nucleic acids, maintaining genome integrity, and defending against viral infections. In C. elegans, piRNA precursors are transcribed in the nucleus and are subjected to a number of processing and maturation steps.

The Functions of Non-coding RNAs in rRNA Regulation.

Ribosomes are ribonucleoprotein machines that decode the genetic information embedded in mRNAs into polypeptides. Ribosome biogenesis is tightly coordinated and controlled from the transcription of pre-rRNAs to the assembly of ribosomes. Defects or disorders in rRNA production result in a number of human ribosomopathy diseases.

The USTC co-opts an ancient machinery to drive piRNA transcription in .

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In , most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis, the mechanism of piRNA transcription remains elusive.