Alternative mRNA transcription, processing, and translation: insights from RNA sequencing
Abstract
The human transcriptome comprises >80,000 protein-coding transcripts and the estimated number of proteins synthesized from these transcripts is in the range of 250,000 to 1 million. These transcripts and proteins are encoded by less than 20,000 genes, suggesting extensive regulation at the transcriptional, post-transcriptional, and translational level. Here we review how RNA sequencing (RNA-seq) technologies have increased our understanding of the mechanisms that give rise to alternative transcripts and their alternative translation. We highlight four different regulatory processes: alternative transcription initiation, alternative splicing, alternative polyadenylation, and alternative translation initiation. We discuss their transcriptome-wide distribution, their impact on protein expression, their biological relevance, and the possible molecular mechanisms leading to their alternative regulation. We conclude with a discussion of the coordination and the interdependence of these four regulatory layers.
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Genes often have alternative TSSs, which are differentially used across tissues.
“Genes often have alternative TSSs, which are differentially used across tissues36–38.”
From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [37]
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Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation
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- Authors
- de Klerk, E., & ‘t Hoen, P. A. C.
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 31
- Issue
- 3
- Pages
- 128-139
- ISSN
- 0168-9525 (ISSN-L)
- OpenAlex
- W2026141529
- Cited by
- 350
- References
- 21
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 31 · 2023: 26 · 2022: 33 · 2021: 38 · 2020: 22 · 2019: 23 · 2018: 31 · 2017: 41 · 2016: 37 · 2015: 20 · 2012: 1
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- alternative splicing, alternative polyadenylation, alternative transcription initiation, alternative translation initiation, splice variants, transcriptome, post-transcriptional regulation, translational regulation, protein expression, RNA-seq
- MeSH terms
- Humans, Promoter Regions, Genetic, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Alternative Splicing, Sequence Analysis, RNA, Gene Expression Profiling, Polyadenylation, High-Throughput Nucleotide Sequencing, Transcriptome
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