RNA secondary structure mediated by Alu insertion as a novel disease-causing mechanism

ABSTRACTWe have recently reported a homozygous Alu insertion variant (termed Alu_Ins) within the 3’-untranslated region (3’-UTR) of the SPINK1 gene as the cause of a new pediatric disease entity. Although Alu-Ins has been shown, by means of a full-length gene expression assay (FLGEA), to result in the complete loss of SPINK1 mRNA expression, the precise underlying mechanism(s) has remained elusive. Herein, we filled this knowledge gap by adopting a hypothesis-driven approach. Employing RepeatMasker, we identified two Alu elements (termed Alu1 and Alu2) within the SPINK1 locus; both are located deep within intron 3 and, most importantly, reside in the opposite orientation to Alu-Ins. Using FLGEA, we provide convincing evidence that Alu-Ins disrupts splicing by forming RNA secondary structures with Alu1 in the pre-mRNA sequence. Our findings reveal a previously undescribed disease-causing mechanism, resulting from an Alu insertion variant, which has implications for Alu detection and interpretation in human disease genes.

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Faculty Opinions recommendation of Systematic screen for human disease genes in yeast.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1008951.116808 ◽

2002 ◽

Author(s):

Andrew Wilkie

Keyword(s):

Human Disease ◽

Disease Genes ◽

Human Disease Genes

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A Survey on Computational Methods for Essential Proteins and Genes Prediction

Current Bioinformatics ◽

10.2174/1574893613666181112150422 ◽

2019 ◽

Vol 14 (3) ◽

pp. 211-225 ◽

Cited By ~ 2

Author(s):

Ming Fang ◽

Xiujuan Lei ◽

Ling Guo

Keyword(s):

Computational Methods ◽

Drug Targets ◽

Disease Genes ◽

Essential Proteins ◽

Experimental Identification ◽

Cellular Life ◽

Different Types ◽

The Stability ◽

Human Disease Genes ◽

Biology Research

Background: Essential proteins play important roles in the survival or reproduction of an organism and support the stability of the system. Essential proteins are the minimum set of proteins absolutely required to maintain a living cell. The identification of essential proteins is a very important topic not only for a better comprehension of the minimal requirements for cellular life, but also for a more efficient discovery of the human disease genes and drug targets. Traditionally, as the experimental identification of essential proteins is complex, it usually requires great time and expense. With the cumulation of high-throughput experimental data, many computational methods that make useful complements to experimental methods have been proposed to identify essential proteins. In addition, the ability to rapidly and precisely identify essential proteins is of great significance for discovering disease genes and drug design, and has great potential for applications in basic and synthetic biology research. Objective: The aim of this paper is to provide a review on the identification of essential proteins and genes focusing on the current developments of different types of computational methods, point out some progress and limitations of existing methods, and the challenges and directions for further research are discussed.

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