Outline

  • Abstract
  • 1. Introduction
  • 2. Structure of Alu and Murine Mobile Elements
  • 3. Alu and Human Genomic Diversity
  • 4. Alu-Mediated Recombination and Insertional Mutagenesis Contribution to Human Diseases
  • 5. Alu Rna Accumulation Induces Age-Related Macular Degeneration (amd)
  • 6. Adar Gene Family and Alu Rna Editing
  • 6.1. Other Cellular Mechanisms That May Deal with Alu Dsrnas
  • 7. Concluding Remarks
  • Acknowledgment
  • References

رئوس مطالب

  • 1. مقدمه
  • 2.ساختار عناصر متحرک Alu و موشی
  • 3.تنوع ژنومی Alu وانسان
  • 4.نوترکیبی به واسطه Alu و نقش جهش دخول در بیماری های انسانی
  • 5.تجمع RNA Alu تخریب ماکولار وابسته به سن (AMD) را القا می کند
  • 6. خانواده ژن ADAR و ویرایش RNA Alu
  • 6.1. دیگر مکانیسم های سلولی که ممکن است در ارتباط با dsRNA های Alu باشند
  • 7. نتیجه گیری

Abstract

Alus, the short interspersed repeated sequences (SINEs), are retrotransposons that litter the human genomes and have long been considered junk DNA. However, recent findings that these mobile elements are transcribed, both as distinct RNA polymerase III transcripts and as a part of RNA polymerase II transcripts, suggest biological functions and refute the notion that Alus are biologically unimportant. Indeed, Alu RNAs have been shown to control mRNA processing at several levels, to have complex regulatory functions such as transcriptional repression and modulating alternative splicing and to cause a host of human genetic diseases. Alu RNAs embedded in Pol II transcripts can promote evolution and proteome diversity, which further indicates that these mobile retroelements are in fact genomic gems rather than genomic junks.


Conclusions

Repeat elements are landscape-determining components of our genome, and they are “hot spots” elements that can affect our health through at least two known different mechanisms: (1) self-propagation and retrotransposition and (2) accumulation and cytotoxicity. Still, several questions remain unresolved: why and how Alu RNAs accumulate in the RPE of GA patients? It is possible that chronic stress insults (oxidative stress, heat shock, viral infection, etc.) in combination with increasing age and senescence induce Alu RNA accumulation [160–163]. Another important question is: are Alu RNAs accumulated in other age-related neurodegenerative diseases? However, some studies have suggested that the central nervous system is a privileged environment for transposition. In addition, DICER1 and the fine tuning of the miRNA gene network have been shown to be crucial for neuronal integrity. Indeed, genetic ablation of DICER1 induces neurodegeneration via hyperphosphorylation of tau protein and activation of ERK1/2 [164, 165]. Furthermore, the NALP3 inflammasome has been shown to be involved in Alzheimer’s disease (AD) [166]. Altered DICER1 and miRNA regulation have been shown to be involved in other neurodegenerative diseases such as Huntington’s [167] and Parkinson’s diseases [168]; however, the Alu RNA profiling has not been reported yet.

The new sequencing technologies combined with rigorous functional analyses are available to study the mobilome, and they will certainly yield more valuable insights into both functional properties of the genomic gems and disease pathogenesis.

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