The human bone morphogenetic protein-1 was originally identified as a protein with the capacity to stimulate bone and cartilage growth in vitro. Its gene sequence identified it as an alternatively spliced human homolog of the Drosophila dorsal-ventral patterning tolloid gene and suggested that it activates transforming growth factor-beta-like molecules by proteolytic cleavage. Its expression pattern and its recently identified activity as a procollagen C proteinase, however, suggest that it has a more general function in the early stages of embryogenesis. This view is strengthened by the previous observation of a third alternatively spliced isoform of the gene, called bone morphogenetic protein 1/His. We now show that the gene is expressed in three additional variants, leading to shorter and slightly modified C-termini. The three variants are preferentially expressed in placenta but show individual differences in their expression profiles in other soft tissues.
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Proc Natl Acad Sci U S A
February 2025
Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901.
In the pregenomic era, scientists were puzzled by the observation that haploid genome size (the C-value) did not correlate well with organismal complexity. This phenomenon, called the "C-value paradox," is mostly explained by the fact that protein-coding genes occupy only a small fraction of eukaryotic genomes. When the first genome sequences became available, scientists were even more surprised by the fact that the number of genes (G-value) was also a poor predictor of complexity, which gave rise to the "G-value paradox.
View Article and Find Full Text PDFLife Med
April 2024
Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China.
As the most prevalent type of alternative splicing in animal cells, exon skipping plays an important role in expanding the diversity of transcriptome and proteome, thereby participating in the regulation of diverse physiological and pathological processes such as development, aging, and cancer. Cellular senescence serving as an anti-cancer mechanism could also contribute to individual aging. Although the dynamic changes of exon skipping during cellular senescence were revealed, its biological consequence and upstream regulator remain poorly understood.
View Article and Find Full Text PDFSci Rep
January 2025
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #04-06 Immunos, Singapore, 138648, Singapore.
The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution.
View Article and Find Full Text PDFNat Commun
January 2025
UK Dementia Research Institute, University of Cambridge, Cambridge, United Kingdom.
Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.
View Article and Find Full Text PDFGastroenterology
January 2025
Faculty of Data Science, Musashino University, 3-3-3 Ariake Koto-ku, Tokyo 135-8181, Japan. Electronic address:
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