Cell differentiation is a process that must be precisely regulated for the maintenance of tissue homeostasis. Differentiation towards a multiciliated cell fate is characterized by well-defined stages, where a transcriptional cascade is activated leading to the formation of multiple centrioles and cilia. Centrioles migrate and dock to the apical cell surface and, acting as basal bodies, give rise to multiple motile cilia. The concerted movement of cilia ensures directional fluid flow across epithelia and defects either in their number or structure can lead to disease phenotypes. Micro-RNAs (miRNAs; miRs) are small, non-coding RNA molecules that play an important role in post-transcriptional regulation of gene expression. miR-34b/c and miR-449a/b/c specifically function throughout the differentiation of multiciliated cells, fine-tuning the expression of many different centriole- and cilia-related genes. They strictly regulate the expression levels of genes that are required both for commitment towards the multiciliated cell fate (e.g. Notch) and for the establishment and maintenance of this fate by regulating the expression of transcription factors and structural components of the pathway. Herein we review miR-34 and miR-449 spatiotemporal regulation along with their roles during the different stages of multiciliogenesis.

中文翻译：

---

在转录后水平微调多细胞分化：miR-34/449家族成员的贡献

细胞分化是一个必须精确调节以维持组织稳态的过程。向多纤毛细胞命运的分化以明确定义的阶段为特征，其中转录级联被激活，导致多个中心粒和纤毛的形成。中心粒迁移并停靠到顶端细胞表面，并作为基体产生多个活动纤毛。纤毛的协同运动确保了流经上皮细胞的定向流体流动，其数量或结构的缺陷都可能导致疾病表型。微小 RNA (miRNA；miR) 是小的非编码 RNA 分子，在基因表达的转录后调控中发挥重要作用。miR-34b/c 和 miR-449a/b/c 在多纤毛细胞的分化过程中特异性发挥作用，微调许多不同中心粒和纤毛相关基因的表达。它们严格调节基因的表达水平，这些基因是致力于多分支细胞命运（例如Notch ) 并通过调节转录因子和通路结构成分的表达来建立和维持这种命运。在这里，我们回顾了 miR-34 和 miR-449 的时空调节以及它们在多纤毛发生的不同阶段的作用。