The potential of engineered eukaryotic RNA‐binding proteins as molecular tools and therapeutics

Shotwell, Carl; Cleary, John D.; Berglund, J. Andrew

doi:10.1002/wrna.1573

Cited by 15 publications

(13 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is clear that RBPs function sequentially to post-transcriptionally regulate gene expression at different steps of myogenesis, in much the similar manner as different myogenic transcription factors that promote myoblast proliferation, myogenic differentiation and satellite cell quiescence at the transcription level. Given the growing number of muscular disorders associated with RNAs and RBPs, understanding the functional implication of RBPs in different steps of muscle development may have the potential to use them as therapeutics ( Shotwell et al, 2020 ). However, there are also many fundamental questions that remain open for further investigations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

Shi

Grifone

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells. Post-transcriptional regulation of gene expression mediated by RNA-binding proteins is critically required for muscle development during embryogenesis and for muscle homeostasis in the adult. Differential subcellular localization and activity of RNA-binding proteins orchestrates target gene expression at multiple levels to regulate different steps of myogenesis. Dysfunctions of these post-transcriptional regulators impair muscle development and homeostasis, but also cause defects in motor neurons or the neuromuscular junction, resulting in muscle degeneration and neuromuscular disease. Many RNA-binding proteins, such as members of the muscle blind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) families, display both overlapping and distinct targets in muscle cells. Thus they function either cooperatively or antagonistically to coordinate myoblast proliferation and differentiation. Evidence is accumulating that the dynamic interplay of their regulatory activity may control the progression of myogenic program as well as stem cell quiescence and activation. Moreover, the role of RNA-binding proteins that regulate post-transcriptional modification in the myogenic program is far less understood as compared with transcription factors involved in myogenic specification and differentiation. Here we review past achievements and recent advances in understanding the functions of RNA-binding proteins during skeletal muscle development, regeneration and disease, with the aim to identify the fundamental questions that are still open for further investigations.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Altogether, these observations definitely illustrate the importance of RBPs-regulated networks in skeletal muscle physiopathology. Thus, they present the potential to be served as clinically relevant disease-related biomarkers and as therapeutics ( Shotwell et al, 2020 ).…”

Section: An Overview Of Post-transcriptional Regulation In Muscle Developmentmentioning

confidence: 99%

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

Shi

Grifone

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…These approaches are mainly explored in humans, in the context of targeted drug delivery therapeutics. Interesting examples are mammalian lipoproteins, which are often proposed for use in human siRNAs delivery [ 244 , 245 , 246 , 247 , 248 , 249 ]. In addition, a high percentage of mammalian extracellular miRNAs are bound to Ago proteins, and pre-assembled siRNA-Ago complexes, delivered via different carriers, can increase the gene silencing effect in mice [ 180 , 181 , 182 , 250 ].…”

Section: Biotechnological Prospectsmentioning

confidence: 99%

RNAs on the Go: Extracellular Transfer in Insects with Promising Prospects for Pest Management

Santos

Remans

Brande

et al. 2021

Plants

View full text Add to dashboard Cite

RNA-mediated pathways form an important regulatory layer of myriad biological processes. In the last decade, the potential of RNA molecules to contribute to the control of agricultural pests has not been disregarded, specifically via the RNA interference (RNAi) mechanism. In fact, several proofs-of-concept have been made in this scope. Furthermore, a novel research field regarding extracellular RNAs and RNA-based intercellular/interorganismal communication is booming. In this article, we review key discoveries concerning extracellular RNAs in insects, insect RNA-based cell-to-cell communication, and plant–insect transfer of RNA. In addition, we overview the molecular mechanisms implicated in this form of communication and discuss future biotechnological prospects, namely from the insect pest-control perspective.

show abstract

“…Of note, these systems are amenable to be combined with regulatory proteins to attain complex dynamic behaviors [16]. A heterologous RRM-containing protein with definite regulatory activity, in addition to provide empirical evidence on the adaptability of such RNA-binding domains to different genetic backgrounds, would enlarge the synthetic biology toolkit [17], boosting applications in which high orthogonality, expression fine-tuning, and signal integrability are required features. In addition, RRMs can themselves be allosterically regulated, opening up new avenues for post-transcriptional regulation by small molecules.…”

Section: Introductionmentioning

confidence: 99%

Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria

Dolcemascolo

Heras-Herandez

Goiriz

et al. 2022

Preprint

View full text Add to dashboard Cite

The RNA recognition motif (RRM) is the most common RNA-binding protein domain identified in nature. However, RRM-containing proteins are only prevalent in eukaryotic phyla, in which they play central regulatory roles. Here, we engineered an orthogonal post-transcriptional control system of gene expression in the bacterium Escherichia coli with the mammalian RNA-binding protein Musashi-1, which is a stem cell marker with neurodevelopmental role that contains two canonical RRMs. In the circuit, Musashi-1 is regulated transcriptionally and works as an allosteric translation repressor thanks to a specific interaction with the leader coding region of a messenger RNA and its structural plasticity to respond to fatty acids. We fully characterized the genetic system at the population and single-cell levels showing a significant fold change in reporter expression, and the underlying molecular mechanism by assessing the in vitro binding kinetics and in vivo functionality of a series of RNA mutants. Moreover, the dynamic response of the system was well recapitulated by a bottom-up mathematical model. This work illustrates how RRM-based regulation can be adapted to simple organisms, thereby paving the way for engineering more complex circuits in prokaryotes by combining transcription and translation control with proteins.

show abstract

The potential of engineered eukaryotic RNA‐binding proteins as molecular tools and therapeutics

Cited by 15 publications

References 159 publications

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

RNAs on the Go: Extracellular Transfer in Insects with Promising Prospects for Pest Management

Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria

Contact Info

Product

Resources

About