senescence acts as a physiological barrier against uncontrolled proliferation of cells with potentially harmful alterations, contributing to tumor suppression and tissue homeostasis in live organisms [1]. Senescence is a complex phenotype that involves major changes in cellular function and structure. This phenotype is characterized by a specific gene expression program, which is controlled by ...

RNase III enzyme Drosha interacts with DGCR8 to form the Microprocessor, initiating canonical microRNA (miRNA) maturation in the nucleus. Here, we re-evaluated where Drosha functions in cells using Drosha and/or DGCR8 knock out (KO) cells and cleavage reporters. Interestingly, a truncated Drosha mutant located exclusively in the cytoplasm cleaved pri-miRNA effectively in a DGCR8-dependent manne...

MicroRNAs (miRNAs) are critical regulators of nervous system function, and in vivo knockout studies have demonstrated that miRNAs are necessary for multiple aspects of neuronal development and survival. However, the role of miRNA biogenesis in the formation and function of synapses in the cerebral cortex is only minimally understood. Here, we have generated and characterized a mouse line with a...

22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of hu...

The ING family of tumor suppressor proteins controls several cellular functions relevant to antitumor protection, such as cell cycle control, apoptosis, senescence, or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognition of histone marks and recruitment of protein complexes with chromatin-modifying activity to sp...

OBJECTIVES The microRNAs have been implicated in the development and function of the inner ear, especially in contribution to hearing. However, the impact of idiopathic sudden sensorineural hearing loss (SSNHL) on expression of miRNA biogenesis-related components has not been established. To investigate the regulations of microRNA (miRNA) biogenesis-related components, argonaute 2 (AGO2) and Di...

RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be...

The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs over...

BACKGROUND Drosha is a nuclear RNase III enzyme that initiates processing of regulatory microRNA. Together with partner protein DiGeorge syndrome critical region 8 (DGCR8), it forms the Microprocessor complex, which cleaves precursor transcripts called primary microRNA to produce hairpin precursor microRNA. In addition to two RNase III catalytic domains, Drosha contains a C-terminal double-stra...

Microprocessor [Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) complex] processing of primary microRNA (pri-miRNA) is the critical first step in miRNA biogenesis, but how the Drosha cleavage site is determined has been unclear. Previous models proposed that the Drosha-DGCR8 complex measures either ~22 nt from the upper stem-single-stranded RNA (ssRNA, terminal loop) junction or ~11 nt ...