RESUMEN
There are more than 150 types of chemical modifications in RNA, mainly methylation, which are widely distributed in all kinds of RNA, including messenger RNA, transfer RNA, ribosomal RNA, non-coding small RNA and long non-coding RNA. In recent years, the identification of RNA methylation modification enzymes and the development of high-throughput sequencing technology at transcriptome level laid a foundation for revealing the expression and function of genes regulated by chemical modification of RNA. In this review, the most recent advances of RNA methylation, especially N6-methyladenosine (m6a) in the blood system, including the regulation of RNA methyltransferases, RNA demethylases and RNA binding proteins on normal and malignant hematopoiesis through the regulation of RNA methylation level were summarized briefly.
Asunto(s)
Adenosina , ARN , Adenosina/análogos & derivados , Adenosina/metabolismo , Hematopoyesis , Humanos , Metilación , ARN/metabolismoRESUMEN
Long noncoding RNAs (lncRNAs) have emerged as important components of gene regulatory network in embryonic stem cells (ESCs). However, the function and molecular mechanism of lncRNAs are still largely unknown. Here we identifies Trincr1 (TRIM71 interacting long noncoding RNA 1) lncRNA that regulates the FGF/ERK signaling and self-renewal of ESCs. Trincr1 is exported by THOC complex to cytoplasm where it binds and represses TRIM71, leading to the downregulation of SHCBP1 protein. Knocking out Trincr1 leads to the upregulation of phosphorylated ERK and ERK pathway target genes and the decrease of ESC self-renewal, while knocking down Trim71 completely rescues the defects of Trincr1 knockout. Furthermore, ectopic expression of Trincr1 represses FGF/ERK signaling and the self-renewal of neural progenitor cells (NPCs). Together, this study highlights lncRNA as an important player in cell signaling network to coordinate cell fate specification.
Asunto(s)
Factores de Crecimiento de Fibroblastos/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Células Madre Embrionarias de Ratones/metabolismo , ARN Largo no Codificante/genética , Factores de Transcripción/genética , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Embrión de Mamíferos , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes , Sistema de Señalización de MAP Quinasas , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Células Madre Embrionarias de Ratones/citología , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Fosforilación , Unión Proteica , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Adaptadoras de la Señalización Shc/genética , Proteínas Adaptadoras de la Señalización Shc/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismoRESUMEN
Embryonic stem cells (ESCs) hold great promises for treating and studying numerous devastating diseases. The molecular basis of their potential is not completely understood. Large noncoding RNAs (lncRNAs) are an important class of gene regulators that play essential roles in a variety of physiologic and pathologic processes. Dozens of lncRNAs are now identified to control ESC self-renewal and differentiation. Research on lncRNAs may provide novel insights into manipulating the cell fate or reprogramming somatic cells into induced pluripotent stem cells (iPSCs). In this review, we summarize the recent research efforts in identifying functional lncRNAs and understanding how they act in ESCs, and discuss various future directions of this field.
Asunto(s)
Células Madre Embrionarias/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Diferenciación Celular , Reprogramación Celular , Células Madre Embrionarias/citología , Regulación de la Expresión Génica , Humanos , MicroARNs/metabolismo , ARN Largo no Codificante/clasificación , Proteínas de Unión al ARN/metabolismoRESUMEN
The miR-294 and miR-302 microRNAs promote the abbreviated G1 phase of the embryonic stem cell (ESC) cell cycle and suppress differentiation induced by let-7. Here, we evaluated the role of the retinoblastoma (Rb) family proteins in these settings. Under normal growth conditions, miR-294 promoted the rapid G1-S transition independent of the Rb family. In contrast, miR-294 suppressed the further accumulation of cells in G1 in response to nutrient deprivation and cell-cell contact in an Rb-dependent fashion. We uncovered five additional miRNAs (miR-26a, miR-99b, miR-193, miR-199a-5p, and miR-218) that silenced ESC self-renewal in the absence of other miRNAs, all of which were antagonized by miR-294 and miR-302. Four of the six differentiation-inducing miRNAs induced an Rb-dependent G1 accumulation. However, all six still silenced self-renewal in the absence of the Rb proteins. These results show that the miR-294/miR-302 family acts through Rb-dependent and -independent pathways to regulate the G1 restriction point and the silencing of self-renewal, respectively.
