Biology subjects

Sun, W.-J.

Publications and source records attributed to Sun, W.-J..

3 recordsLinked to original sources

bioRxiv2025

RAB23 Modulates Signaling Protein Ciliary Homeostasis through Promoting RAB18-mediated Inward BBSome Transition Zone Passage

As an intraflagellar transport (IFT) cargo adaptor, the BBSome targets the basal body region located just below the transition zone (TZ) before proceeding to cross the TZ for ciliary entry. This process of TZ crossing crucially governs BBSome presence and quantity available for signaling protein coupling within cilia, influencing the dynamic behavior of signaling proteins in cilia by controlling their ciliary removal. Our previous study revealed that the GTPase RAB18 binds to its BBSome effector in the basal bodies right below the TZ and recruits the BBSome to cross the TZ for ciliary entry by lateral transport between the plasma and ciliary membranes. However, the mechanism by which RAB18 is activated to accomplish this function has remained elusive. This study uncovers that, under physiological conditions, Chlamydomonas RAB23 in its GDP-bound state (RAB23-GDP) predominantly localizes to the same basal body region as RAB18-GDP and activates RAB18-GDP as a RAB18-specific guanine nucleotide exchange factor. RAB18-GDP attaches to the membrane and binds to the BBSome. This interaction occurs independently of anterograde IFT association, allowing the BBSome to diffuse through the TZ and enter cilia. Subsequently, RAB23-GDP facilitates its own ciliary entry by binding to the RAB18-GTP/BBSome entity as a BBSome cargo. Our findings establish a model where the BBSome enters cilia through the RAB23-RAB18 module-mediated inward BBSome TZ diffusion pathway. According to this model, hedgehog signaling defects caused by rab23 mutations could induce Carpenter syndrome in humans, providing a mechanistic understanding behind the inward BBSome TZ passage required for proper ciliary signaling. Significance statementCertain ciliary signaling proteins are removed from cilia through the outward BBSome transition zone (TZ) diffusion pathway. The inward BBSome TZ crossing is orchestrated by RAB18. The current study unveils that RAB23 in its GDP-bound state (RAB23-GDP) and RAB18-GDP predominantly localize to the same basal body region located just below the TZ. RAB23-GDP activates RAB18-GDP as a RAB18-specific guanine nucleotide exchange factor. RAB18-GTP subsequently recruits the BBSome as its effector to cross the TZ for ciliary entry. Following this, RAB23-GDP enters cilia as a BBSome cargo. The regulatory interplay between RAB23 and RAB18, with RAB23 promoting inward BBSome TZ crossing via RAB18, establishes a molecular mechanism for the BBSome-dependent retrieval of signaling proteins from cilia.

cell biology↗

bioRxiv2021

Copy number variation profile-based genomic subtyping of premenstrual dysphoric disorder in Chinese

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. The symptomatic heterogeneity, along with largely unknown genetics, of PMDD have greatly hindered its effective treatment. In the present study, 127 Chinese PMDD patients of the invasion and depression subtypes clinically differentiated by us earlier were analyzed together with 108 non-PMDD controls for genome-wide copy number variations (CNVs). Germline genomic DNA samples from white blood cells were subjected to AluScan sequencing-based CNV profiling, which enabled clustering of patient samples readily into the V and D groups, dominated by the "invasion" and "depression" clinical subtypes, respectively; the CNVs obtained with 100-kb windows yielded two clusters that were correlated with these subtypes with a consistency of up to 89.8%. Diagnostic correlation- and frequency-based CNV features of either CNV-gain (CNVG) or CNV-loss (CNVL) that could differentiate between V and D subtypes were selected and analyzed. CNVG features located preferentially in S2-phase replicating regions and enriched with steroid hormone biosynthesis pathway of genes were found protective against PMDD. Moreover, machine learning employing the correlation-based CNV features could predict with >80% accuracy whether a genomic sample was D-type, V-type or control. In terms of their CNV profiles, the D- and V-types differed more from one another than from the controls, thereby providing a genomic basis for the clinical D-V subtyping of PMDD. Genome-wide profiling of CNVs, as a new approach to complex disease genetics, has revealed recurrent CNVs and genomic features beyond individual genes and mutations underlying PMDD clinical diversity.

genomics↗

bioRxiv2017

Discovering the Interactions between Circular RNAs and RNA-binding Proteins from CLIP-seq Data using circScan

Although tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only few of them have been characterized with biological functions. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs) by discovering back-splicing reads from Cross-Linking and Immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. By using our method, we have systematically scanned ~1500 CLIP-seq datasets, and identified ~12540 and ~1090 novel circRNA-RBP interactions in human and mouse genomes, respectively, which include all known interactions between circRNAs and Argonaute (AGO) proteins. More than twenty novel interactions were further experimentally confirmed by RNA Immunoprecipitation quantitative PCR (RIP-qPCR). Importantly, we uncovered that some natural circRNAs interacted with cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-Methyladenosine (m6A), indicating they can be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs, suggesting they may play important roles in diverse biological processes.

molecular biology↗