Ozisin M Samil, Imren Gozde, Aydin Busra, Karaosmanoglu Beren, Taskiran Ekim Z
Institute of Health Sciences, Department of Medical and Surgical Research, Hacettepe University, Ankara, Turkey.
Faculty of Medicine, Department of Medical Genetics, Hacettepe University, Sihhiye, Ankara, Turkey.
Mol Biol Rep. 2025 Jan 13;52(1):120. doi: 10.1007/s11033-024-10216-1.
La-related protein 7 (LARP7) is a key regulator of RNA metabolism and is thought to play a role in various cellular processes. LARP7 gene autosomal recessive mutations are the cause of Alazami syndrome, which presents with skeletal abnormalities, intellectual disabilities, and facial dysmorphisms. This study aimed to determine the role of LARP7 in modulating gene expression dynamics during osteogenesis.
First, the temporal expression profile of the LARP7 gene during various stages of osteogenesis was examined. Then, RNA interference-mediated knockdown of LARP7 was implemented and high-throughput RNA-seq analysis was performed in order to identify global gene expression changes associated with knockdown of LARP7. The findings show there were significant alterations in the overall gene expression profile. The observed down-regulation in extracellular matrix (ECM) component genes suggests that it might lead to impairments in the structure and function of the bone matrix. Additionally, modulation of alternative splicing events were observed, especially in the RUNX2 and SPP1, indicating the potential contribution of LARP7 to the phenotypic features observed in Alazami syndrome.
Overall, the findings clarify the regulatory mechanisms of LARP7 in osteogenic differentiation and illuminate potential avenues for therapeutic interventions in patients with skeletal disorders.
La相关蛋白7（LARP7）是RNA代谢的关键调节因子，被认为在多种细胞过程中发挥作用。LARP7基因的常染色体隐性突变是阿拉扎米综合征的病因，该综合征表现为骨骼异常、智力残疾和面部畸形。本研究旨在确定LARP7在成骨过程中调节基因表达动态方面的作用。
首先，检测了LARP7基因在成骨各个阶段的时间表达谱。然后，实施RNA干扰介导的LARP7敲低，并进行高通量RNA测序分析，以确定与LARP7敲低相关的整体基因表达变化。研究结果表明，整体基因表达谱存在显著改变。观察到细胞外基质（ECM）成分基因的下调，这表明可能会导致骨基质的结构和功能受损。此外，还观察到可变剪接事件的调节，特别是在RUNX2和SPP1中，这表明LARP7对阿拉扎米综合征中观察到的表型特征具有潜在贡献。
总体而言，这些发现阐明了LARP7在成骨分化中的调节机制，并为骨骼疾病患者的治疗干预指明了潜在途径。
