Biology subjects

Chan, T. W.

Publications and source records attributed to Chan, T. W..

3 recordsLinked to original sources

bioRxiv2026

Massive programmed DNA elimination during embryogenesis in the trioecious nematode Auanema rhodense

In animals, the germline is usually set aside early in development and its genome is protected to ensure faithful transmission of genetic information to future generations. Genetic alterations in somatic cells are not inherited by progeny, and the somatic genome does not have to be protected from change in the same way. In some species, programmed DNA elimination (PDE) results in the directed loss of genetic material from somatic cells. Here, we report extreme PDE in Auanema rhodense, a free-living nematode with a remarkable, trioecious life history and unusual patterns of sex chromosome inheritance. We find that nearly two thirds of the A. rhodense germline genome is eliminated from somatic cells, with DNA lost from chromosome ends as well as within chromosomes, resulting in fragmentation of the seven germline chromosomes into fourteen somatic chromosomes. Most eliminated DNA comprises multi-megabase tandem repeat blocks. Eliminated DNA on the X chromosome harbours germline-restricted repeats that are distinct from those on the autosomes. The eliminated DNA includes many highly-repeated non-coding RNA loci but few protein-coding genes. Elimination sites are strongly associated with a palindromic sequence motif that likely directs DNA breakage and new telomere repeat array addition. Cytologically, PDE begins at the 12-cell stage of embryogenesis, is synchronous across all chromosomes, and is characterised by the formation of transient micronucleus-like bodies. Together, these findings reveal unusually extensive PDE in a free-living nematode and raise the possibility that germline-restricted repeat architecture may contribute to the atypical sex chromosome inheritance observed in Auanema.

genomics↗

bioRxiv2023

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity

RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing. In this study, we identify hnRNPM as an essential RNA binding protein that suppresses cryptic splicing through binding to deep introns, preserving transcriptome integrity. Long interspersed nuclear elements (LINEs) harbor large amounts of pseudo splice sites in introns. hnRNPM preferentially binds at intronic LINEs and represses LINE-containing pseudo splice site usage for cryptic splicing. Remarkably, a subgroup of the cryptic exons can form long dsRNAs through base-pairing of inverted Alu transposable elements scattered in between LINEs and trigger interferon immune response, a well-known antiviral defense mechanism. Notably, these interferon-associated pathways are found to be upregulated in hnRNPM-deficient tumors, which also exhibit elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity. Targeting hnRNPM in tumors may be used to trigger an inflammatory immune response thereby boosting cancer surveillance.

genomics↗

bioRxiv2022

scAllele: a versatile tool for the detection and analysis of variants in scRNA-seq

Single-cell RNA sequencing (scRNA-seq) data contain rich information at the gene, transcript, and nucleotide levels. Most analyses of scRNA-seq have focused on gene expression profiles, and it remains challenging to extract nucleotide variants and isoform-specific information. Here, we present scAllele, an integrative approach that detects single nucleotide variants, insertions, deletions, and their allelic linkage with splicing patterns in scRNA-seq. We demonstrate that scAllele achieves better performance in identifying nucleotide variants than other commonly used tools. In addition, the read-specific variant calls by scAllele enables allele-specific splicing analysis, a unique feature not afforded by other methods. Applied to a lung cancer scRNA-seq data set, scAllele identified variants with strong allelic linkage to alternative splicing, some of which being cancer-specific. scAllele represents a versatile tool to uncover multi-layer information and novel biological insights from scRNA-seq data.

bioinformatics↗