Computational discovery of internal micro-exons
Open accessAbstract
Very short exons, also known as micro-exons, occur in large numbers in some eukaryotic genomes. Existing annotation tools have a limited ability to recognize these short sequences, which range in length up to 25 bp. Here, we describe a computational method for the identification of micro-exons using near-perfect alignments between cDNA and genomic DNA sequences. Using this method, we detected 319 micro-exons in 4 complete genomes, of which 224 were previously unknown, human (170), the nematode Caenorhabditis elegans (4), the fruit fly Drosophila melanogaster (14), and the mustard plant Arabidopsis thaliana (36). Comparison of our computational method with popular cDNA alignment programs shows that the new algorithm is both efficient and accurate. The algorithm also aids in the discovery of micro-exon-skipping events and cross-species micro-exon conservation.
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Microexons, defined as 3-27 nucleotide exons, have been largely missed by genome annotations and transcriptome profiling studies, especially those shorter than 15 nucleotides.
“In particular, microexons (Beachy et al., 1985; Coleman et al., 1987), defined here as 3-27 nucleotide (nt)-long exons, have been largely missed by genome annotations and transcriptome profiling studies (Volfovsky et al., 2003; Wu et al., 2013; Wu and Watanabe, 2005). This is especially true for microexons shorter than 15 nts.”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Volfovsky et al., 2003
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Parada, G. E., Munita, R., Georgakopoulos‐Soares, I., Fernandes, H. J. R., Kedlian, V. R., Metzakopian, E., Andrés, M. E., Miska, E. A., & Hemberg, M. (2021) · Figshare · doi:10.6084/m9.figshare.13633004
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212106
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N. E., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212109
Parada, G. E., Munita, R., Georgakopoulos‐Soares, I., Fernandes, H. J. R., Kedlian, V. R., Metzakopian, E., Andrés, M. E., Miska, E. A., & Hemberg, M. (2021) · Figshare · doi:10.6084/m9.figshare.13632980
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212118
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212091
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212085
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212103
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212115
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212097
Olson, P. D., Tracey, A., Baillie, A., James, K., Doyle, S. R., Buddenborg, S. K., Rodgers, F. H., Holroyd, N., & Berriman, M. (2020) · Figshare · doi:10.6084/m9.figshare.13212112
Nelson, D. R., & Syed, K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041979
Spatiotemporal isoform profiling identifies a central activator of microexon splicing in C. elegansPreprint
Koterniak, B., Liang, E., Zoberman, M., He, C., Choudhary, B. C., Sadek, N. H., Pilaka, P. P., Norris, A. D., & Calarco, J. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.14.751627
Blue, R. E., Black, A. J., Cote, J. L., Addish, S. A., Kavalipati, A., Lyons, S. P., Ezzell, J. A., Bremmer, S. C., Dominguez, D., & Giudice, J. (2026) · iScience · doi:10.1016/j.isci.2026.117799
- Authors
- Volfovsky, N., Haas, B. J., & Salzberg, S. L.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-06
- Volume
- 13
- Issue
- 6a
- Pages
- 1216-1221
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC403649
- OpenAlex
- W2161136120
- Cited by
- 87
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 15 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9980088)
- National Institutes of Health
- U.S. National Library of Medicine (R01LM006845, R01-LM 06845)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- exon identification, genome annotation, alternative splicing, cross-species conservation, human genome, Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana
- MeSH terms
- Animals, Base Sequence, DNA, Drosophila melanogaster, Exons, Humans, Molecular Sequence Data, Sequence Alignment, Caenorhabditis elegans, Arabidopsis, Alternative Splicing, DNA, Complementary, DNA, Helminth, DNA, Plant, Computational Biology
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