In the last years, numerous studies have focused on understanding the metabolism of RNA and its implication in disease processes but abnormal RNA metabolism is still unknown. RNA plays a central role in translating genetic information into proteins and in many other catalytic and regulatory tasks. Recent advances in the study of RNA metabolism revealed complex pathways for the generation and maintenance of functional RNA in amyotrophic lateral sclerosis (ALS). Interestingly, perturbations in RNA processing have been described in ALS at various levels such as gene transcription, mRNA stabilization, transport, and translational regulations. In this paper, we will discuss the alteration of RNA profile in ALS disease, starting from transcription, the first step leading to gene expression, through the posttranscriptional regulation, including RNA/DNA binding proteins and aberrant exon splicing to protein noncoding RNAs, as lncRNA and microRNA. 1. Introduction In last decade, many studies have focused on understanding the RNA metabolism and its implication in both translational and regulatory aspect of disease processes. Currently, it is proved that RNA plays a central role in many cellular processes from translating genetic information into proteins, to catalytic and regulatory aspects. Recent advances in the study of RNA metabolism revealed complex pathways in the generation and maintenance of functional RNA and in cells survival related to defects in RNA. Mainly we may distinguish two principal families of RNA, coding (mRNA) and noncoding (miRNA and lncRNA), that are implicated in RNA metabolism that can produce cellular defects and can be causes of diseases. Changes in gene expression and splicing patterns are described in an increasing number of complex diseases such as the neurodegeneratives [1]. Perturbations in RNA processing have been described also in ALS at various levels such as gene transcription, mRNA stabilization, and transport and translational regulation [2]. As for coding RNA, recently changes in gene expression in ALS patients have been demonstrated [3] and the discoveries of mutations in key RNA binding proteins involved in ALS have firmly placed the RNA metabolism as a central process to disease etiology [4, 5]. Moreover, pre-mRNAs alternative splicing represents an important step of posttranscriptional gene regulation by increasing the coding capacity of transcripts, and abnormalities in the RNA splicing in ALS are already known [6, 7]. About noncoding RNA, recent genome-wide analysis of the human transcriptome has revealed a plethora
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