Translating the genome in time and space: Specialized ribosomes, RNA regulons, and RNA-binding proteins
Abstract
A central question in cell and developmental biology is how the information encoded in the genome is differentially interpreted to generate a diverse array of cell types. A growing body of research on posttranscriptional gene regulation is revealing that both global protein synthesis rates and the translation of specific mRNAs are highly specialized in different cell types. How this exquisite translational regulation is achieved is the focus of this review. Two levels of regulation are discussed: the translation machinery and cis-acting elements within mRNAs. Recent evidence shows that the ribosome itself directs how the genome is translated in time and space and reveals surprising functional specificity in individual components of the core translation machinery. We are also just beginning to appreciate the rich regulatory information embedded in the untranslated regions of mRNAs, which direct the selective translation of transcripts. These hidden RNA regulons may interface with a myriad of RNA-binding proteins and specialized translation machinery to provide an additional layer of regulation to how transcripts are spatiotemporally expressed. Understanding this largely unexplored world of translational codes hardwired in the core translation machinery is an exciting new research frontier fundamental to our understanding of gene regulation, organismal development, and evolution.
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RPL3L is prevalent in resting skeletal muscle tissue; following hypertrophic overload, RPL3L expression plummets and is replaced by the ubiquitous isoform RPL3.
“This is characterized by the striated muscle-specific paralog RPL3L, which is prevalent in resting tissue. Following hypertrophic overload, RPL3L expression plummets and is replaced by the ubiquitous isoform RPL3.”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [187]
The RPL3L-to-RPL3 paralog switch enables RPL3-containing ribosomes to physically anchor to mitochondria, maximizing local ATP supply required for hypertrophy, rather than altering mRNA selectivity for contractile proteins.
“Rather than altering mRNA selectivity for contractile proteins, this paralog switch enables the RPL3-containing ribosomes to physically anchor to mitochondria, maximizing the local ATP supply required to sustain the massive energetic cost of hypertrophy [187,189].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [187]
Variation in ribosomal protein composition and rRNA modification patterns may generate ribosome populations with distinct translational preferences.
“More recent work, however, has proposed that variation in ribosomal protein composition and rRNA modification patterns may generate ribosome populations with distinct translational preferences [186,187].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [187]
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- Authors
- Shi, Z., & Barna, M.
- Affiliations
- Stanford University (US)
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 2015-11-13
- Volume
- 31
- Issue
- 1
- Pages
- 31-54
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- OpenAlex
- W2132392209
- Cited by
- 205
- References
- 130
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 16 · 2023: 17 · 2022: 14 · 2021: 21 · 2020: 24 · 2019: 22 · 2018: 31 · 2017: 17 · 2016: 14 · 2015: 2
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DP2OD008509)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- translational regulation, post-transcriptional regulation, specialized ribosomes, RNA-binding proteins, cis-regulatory elements, mRNA untranslated regions, cell type-specific translation, spatiotemporal gene expression, cell differentiation
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Ribosomes, RNA, RNA, Messenger, Protein Biosynthesis, RNA-Binding Proteins, Genome, Regulon
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