bims-meglyc 2024-12-15 papers

Issue of 2024–12–15
two papers selected by
Silvia Radenkovic, UMC Utrecht

J Hum Genet. 2024 Dec 10.

Intron retention caused by a canonical splicing variant in SSR4-related congenital disorder of glycosylation.

Quanquan Wang, Guangyu Wang, Bing Liang, Chen Zhang, Chuanzhu Yan, Pengfei Lin, Ling Li.

Congenital disorder of glycosylation type Iy (CDG-Iy) is an X-linked monogenic inherited disease caused by variants in the SSR4 gene. To date, a total of 11 variants have been identified in 14 CDG-Iy patients. Our study identified a novel canonical splicing variant, c.67+2T>C, in the SSR4 gene (according to the transcript NM_006280.3) in a Chinese CDG-Iy family. Functional analysis revealed that the c.67+2T>C variant induced the retention of the first 46 bp of intron 1 via the recognition of the downstream GC dinucleotide as a non-canonical cryptic donor splice site. This aberrant mRNA splicing resulted in the occurrence of a premature termination codon, triggered nonsense-mediated mRNA decay, and decreased the SSR4 gene expression. Our study is the first to identify aberrant mRNA processing in SSR4-related CDG-Iy and further emphasizes the activation of the non-canonical GC donor splice site in aberrant mRNA processing caused by splicing variants.

DOI: https://doi.org/10.1038/s10038-024-01309-7

Biochem Soc Trans. 2024 Dec 10. pii: BST20240257. [Epub ahead of print]

Tools and techniques for quantitative glycoproteomic analysis.

Siyuan Kong, Wei Zhang, Weiqian Cao.

Recent advances in mass spectrometry (MS)-based methods have significantly expanded the capabilities for quantitative glycoproteomics, enabling highly sensitive and accurate quantitation of glycosylation at intact glycopeptide level. These developments have provided valuable insights into the roles of glycoproteins in various biological processes and diseases. In this short review, we summarize pertinent studies on quantitative techniques and tools for site-specific glycoproteomic analysis published over the past decade. We also highlight state-of-the-art MS-based software that facilitate multi-dimension quantification of the glycoproteome, targeted quantification of specific glycopeptides, and the analysis of glycopeptide isomers. Additionally, we discuss the potential applications of these technologies in clinical biomarker discovery and the functional characterization of glycoproteins in health and disease. The review concludes with a discussion of current challenges and future perspectives in the field, emphasizing the need for more precise, high-throughput and efficient methods to further advance quantitative glycoproteomics and its applications.

Keywords: intact glycopeptide; mass spectrometry; quantitative glycoproteomics; quantitative tools

DOI: https://doi.org/10.1042/BST20240257