Arancio Walter, Giordano Carla, Pizzolanti Giuseppe
Section of Endocrinology, Diabetology & Metabolism, Dipartimento Biomedico di Medicina Interna e Specialistica (Di,Bi,M,I,S,), University of Palermo, Piazza delle Cliniche 2, Palermo, 90127, Italy.
J Clin Bioinforma. 2013 Jan 14;3(1):2. doi: 10.1186/2043-9113-3-2.
Hutchinson-Gilford progeria syndrome is a rare dominant human disease of genetic origin. The average life expectancy is about 20 years, patients' life quality is still very poor and no efficient therapy has yet been developed. It is caused by mutation of the LMNA gene, which results in accumulation in the nuclear membrane of a particular splicing form of Lamin-A called progerin. The mechanism by which progerin perturbs cellular homeostasis and leads to the symptoms is still under debate.Micro-RNAs are able to negatively regulate transcription by coupling with the 3' UnTranslated Region of messenger RNAs. Several Micro-RNAs recognize the same 3' UnTranslated Region and each Micro-RNA can recognize multiple 3' UnTranslated Regions of different messenger RNAs. When different messenger RNAs are co-regulated via a similar panel of micro-RNAs, these messengers are called Competing Endogenous RNAs, or ceRNAs.The 3' UnTranslated Region of the longest LMNA transcript was analysed looking for its ceRNAs. The aim of this study was to search for candidate genes and gene ontology functions possibly influenced by LMNA mutations that may exert a role in progeria development.
11 miRNAs were isolated as potential LMNA regulators. By computational analysis, the miRNAs pointed to 17 putative LMNA ceRNAs. Gene ontology analysis of isolated ceRNAs showed an enrichment in RNA interference and control of cell cycle functions.
This study isolated novel genes and functions potentially involved in LMNA network of regulation that could be involved in laminopathies such as the Hutchinson-Gilford progeria syndrome.
哈钦森-吉尔福德早衰综合征是一种罕见的遗传性显性人类疾病。平均预期寿命约为20岁，患者生活质量仍然很差，尚未开发出有效的治疗方法。它由LMNA基因突变引起，该突变导致一种称为早老素的特定剪接形式的核纤层蛋白A在核膜中积累。早老素扰乱细胞稳态并导致症状的机制仍在争论中。
微小RNA能够通过与信使RNA的3'非翻译区结合来负调控转录。几种微小RNA识别相同的3'非翻译区，并且每个微小RNA可以识别不同信使RNA的多个3'非翻译区。当不同的信使RNA通过一组相似的微小RNA共同调控时，这些信使被称为竞争性内源RNA，或ceRNA。
分析了最长LMNA转录本的3'非翻译区以寻找其ceRNA。本研究的目的是寻找可能受LMNA突变影响的候选基因和基因本体功能，这些突变可能在早衰症发展中起作用。
分离出11种miRNA作为潜在的LMNA调节剂。通过计算分析，这些miRNA指向17个推定的LMNA ceRNA。对分离出的ceRNA进行基因本体分析显示，RNA干扰和细胞周期功能控制方面存在富集。
本研究分离出了可能参与LMNA调控网络的新基因和功能，这些基因和功能可能与诸如哈钦森-吉尔福德早衰综合征等核纤层蛋白病有关。
