Molecular Mechanisms in Pentanucleotide Repeat Diseases

Loureiro, Joana; Castro, A C Meira; Figueiredo, Ana Sofia; Silveira, Isabel

doi:10.3390/cells11020205

Cited by 19 publications

(23 citation statements)

References 185 publications

(360 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IDRs are characterized by low amino acid complexity (LC), absence of hydrophobic residues, and enrichment in charged residues [ 147 ]. The regions with a low amino acid complexity (low-complexity domains, LCDs) may contain poly-glutamine and poly-alanine tracts and seem to favor the structuration of ribonucleoprotein complexes [ 148 , 149 , 150 ].…”

Section: Post-transcriptional Regulation Of Gene Expression In the Ne...mentioning

confidence: 99%

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration

Schiera

Schirò

Liegro

2022

IJMS

View full text Add to dashboard Cite

A central aspect of nervous system development and function is the post-transcriptional regulation of mRNA fate, which implies time- and site-dependent translation, in response to cues originating from cell-to-cell crosstalk. Such events are fundamental for the establishment of brain cell asymmetry, as well as of long-lasting modifications of synapses (long-term potentiation: LTP), responsible for learning, memory, and higher cognitive functions. Post-transcriptional regulation is in turn dependent on RNA-binding proteins that, by recognizing and binding brief RNA sequences, base modifications, or secondary/tertiary structures, are able to control maturation, localization, stability, and translation of the transcripts. Notably, most RBPs contain intrinsically disordered regions (IDRs) that are thought to be involved in the formation of membrane-less structures, probably due to liquid–liquid phase separation (LLPS). Such structures are evidenced as a variety of granules that contain proteins and different classes of RNAs. The other side of the peculiar properties of IDRs is, however, that, under altered cellular conditions, they are also prone to form aggregates, as observed in neurodegeneration. Interestingly, RBPs, as part of both normal and aggregated complexes, are also able to enter extracellular vesicles (EVs), and in doing so, they can also reach cells other than those that produced them.

show abstract

Section: Post-transcriptional Regulation Of Gene Expression In the Ne...mentioning

confidence: 99%

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration

Schiera

Schirò

Liegro

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Incorrect or abnormal phase separation of biological macromolecules is closely related to the occurrence of many types of diseases, such as cancer, neurodegenerative diseases, and infectious diseases [ 41 , 42 , 43 ]. The formation and regulation of aberrant biomolecular condensates is changing the way people think about coping with many diseases, including tumor genesis, diagnosis, and treatment.…”

Section: Mechanisms Of Phase Separation In Tumorigenesismentioning

confidence: 99%

Protein Phase Separation: New Insights into Carcinogenesis

Luo

Xiang

Feng

2022

Cancers

View full text Add to dashboard Cite

Phase separation is now acknowledged as an essential biologic mechanism wherein distinct activated molecules assemble into a different phase from the surrounding constituents of a cell. Condensates formed by phase separation play an essential role in the life activities of various organisms under normal physiological conditions, including the advanced structure and regulation of chromatin, autophagic degradation of incorrectly folded or unneeded proteins, and regulation of the actin cytoskeleton. During malignant transformation, abnormally altered condensate assemblies are often associated with the abnormal activation of oncogenes or inactivation of tumor suppressors, resulting in the promotion of the carcinogenic process. Thus, understanding the role of phase separation in various biological evolutionary processes will provide new ideas for the development of drugs targeting specific condensates, which is expected to be an effective cancer therapy strategy. However, the relationship between phase separation and cancer has not been fully elucidated. In this review, we mainly summarize the main processes and characteristics of phase separation and the main methods for detecting phase separation. In addition, we summarize the cancer proteins and signaling pathways involved in phase separation and discuss their promising future applications in addressing the unmet clinical therapeutic needs of people with cancer. Finally, we explain the means of targeted phase separation and cancer treatment.

show abstract

“…Expansions of pyrimidine-rich CCTG, ATTCT and ATTTT/ATTTC repeats are associated with myotonic dystrophy type 2 (DM2) [27] , spinocerebellar ataxia type 10 (SCA10) [28] , and SCA37 and six subtypes of familial adult myoclonic epilepsy (FAME) [29] , respectively. An earlier chemical/enzymatic probing study showed the hairpin formation propensity of CCTG repeats [30] , and a subsequent NMR study revealed that CCTG repeats formed hairpin and dumbbell structures [31] .…”

Section: Introductionmentioning

confidence: 99%