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1.
Nat Rev Mol Cell Biol ; 20(11): 715, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506602

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nat Rev Mol Cell Biol ; 18(5): 331-337, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28270684

RESUMO

Transcription and chromatin function are regulated by proteins that bind to DNA, nucleosomes or RNA polymerase II, with specific non-coding RNAs (ncRNAs) functioning to modulate their recruitment or activity. Unlike ncRNAs, nascent pre-mRNA was considered to be primarily a passive player in these processes. In this Opinion article, we describe recently identified interactions between nascent pre-mRNAs and regulatory proteins, highlight commonalities between the functions of nascent pre-mRNA and nascent ncRNA, and propose that both types of RNA have an active role in transcription and chromatin regulation.


Assuntos
Cromatina/metabolismo , Transcrição Gênica , Animais , Núcleo Celular/metabolismo , Regulação da Expressão Gênica , Humanos , Splicing de RNA , Proteínas Repressoras/metabolismo , Elongação da Transcrição Genética , Fatores de Transcrição
3.
Biomedicines ; 11(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37509532

RESUMO

Circular RNAs (circRNAs), covalently closed RNAs that originate from back-splicing events, participate in the control of several processes, including those that occur in the development of pathological conditions such as cancer. Hereby, we describe circAFF1, a circular RNA overexpressed in alveolar rhabdomyosarcoma. Using RH4 and RH30 cell lines, a classical cell line models for alveolar rhabdomyosarcoma, we demonstrated that circAFF1 is a cytoplasmatic circRNA and its depletion impacts cell homeostasis favouring cell migration through the downregulation of genes involved in cell adhesion pathways. The presented data underline the importance of this circular RNA as a new partial suppressor of the alveolar rhabdomyosarcoma tumour progression and as a putative future therapeutic target.

4.
Nat Commun ; 14(1): 1898, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019933

RESUMO

N6-Methyladenosine (m6A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m6A regulatory network. DDX5 and the m6A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity.


Assuntos
RNA Circular , Rabdomiossarcoma , Humanos , RNA Circular/metabolismo , RNA/metabolismo , Splicing de RNA , Fatores de Processamento de RNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , RNA Helicases DEAD-box/metabolismo
5.
Genes (Basel) ; 12(7)2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203273

RESUMO

Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target.


Assuntos
Ciclo Celular/genética , RNA Circular/genética , RNA/genética , Rabdomiossarcoma Alveolar/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Mioblastos/metabolismo , Proteína Oncogênica v-akt/genética , Splicing de RNA/genética , Rabdomiossarcoma Alveolar/patologia
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