TERRA و بیماری‌های انسانی مرتبط با آن

نوع مقاله : Review Article

نویسندگان

1 دانشجوی کارشناسی ارشد، مرکز تحقیقات بیماری‌های ارثی کودکان، پژوهشکده‌ی پیشگیری اولیه از بیماری‌های غیر واگیر و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 استادیار، مرکز تحقیقات بیماری‌های ارثی کودکان، پژوهشکده‌ی پیشگیری اولیه از بیماری‌های غیر واگیر و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

تلومرها، انتهای فیزیکی کروموزوم‌های خطی را تشکیل می‌دهند و عملکرد آن‌ها به منظور نگهداری پایداری کروموزومی ضروری می‌باشد. در صورت از دست رفتن عملکرد تلومرها، ظرفیت همانندسازی سلولی کاهش می‌یابد و در نهایت، منجر به پیری سلولی و بیماری‌های مرتبط با نقص در احیای اندام و بازسازی بافت (سندرم‌های تلومر) می‌گردد. از سوی دیگر، سرطان‌ها نیز می‌توانند در نتیجه‌ی ناپایداری‌های ژنومی ناشی از اختلال در عملکرد تلومر ایجاد شوند. تاکنون دو نوع مکانیسم‌های نگهداری طول تلومر (TMM یا Telomere maintenance mechanism) شناسایی شده‌اند که شامل تلومراز و ALT (Alternative lengthening of telomeres) می‌باشد. در نئوپلازی‌ها، مکانیسم‌های نگهداری طول تلومر (TMM) می‌توانند به پیش‌بینی بیماری کمک نمایند و احتمال می‌رود در آینده باعث درمان مستقیم شوند. در طی مطالعات اخیر، مشخص شد که تلومرهای یوکاریوتی رونویسی می‌شوند و به رونوشت آن‌ها TERRA (Telomeric repeat-containing RNA) می‌گویند. به طور کلی، افزایش میزان رونویسی از TERRA با کوتاه شدن طول تلومر مرتبط می‌باشد و در عملکرد تلومر تأثیرگذار است. در این مقاله، به طور خلاصه اصول کلی بیماری‌های مرتبط با اختلال در عملکرد تلومر بررسی شده ‌است. به علاوه، در مورد ارتباطات شناخته شده بین رونوشت تلومر (TERRA) و بیماری‌ها بحث شده است. در نهایت، پتانسیل TERRA در رویکرد‌های درمانی بیماری‌های مرتبط با نقص در عملکرد تلومر مورد بررسی قرار گرفته است.

کلیدواژه‌ها

عنوان مقاله [English]

Telomeric Repeat-Containing RNA (TERRA) and Human Diseases

نویسندگان [English]

  • Sepideh Dashti 1
  • Majid Kheirollahi 2
1 MSc Student, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Telomeres are the physical ends of linear chromosomes that maintain chromosomal stability. Loss of telomere function can lead to decrease in replication capacity, cellular senescence and progeria syndromes. In addition, cancer can be developed as a result of the genomic instability associated with telomere dysfunction. Till now, two types of telomere maintenance mechanism (TMM) have been known. The only two telomere maintenance mechanisms that have been described in mammalian cells are an enzymatic method that employs telomerase and recombination-based alternative lengthening of telomeres (ALT). In neoplasia, telomere maintenance mechanisms can be prognostic and may direct therapy in the future. Recently, a class of noncoding telomeric repeat-containing RNA (TERRA or TelRNA) transcripts has been transcribed from telomeres. Generally, increased TERRA transcription is associated with telomere shortening. In this review, we briefly evaluated the general principles behind telomere dysfunction. Moreover, the relationship between TERRA and disease has been described. Finally, TERRA potential in therapeutic approaches associated with defects in telomere function is studied.

کلیدواژه‌ها [English]

  • Telomere
  • Telomeric repeat-containing RNA (TERRA)
  • Telomere maintenance mechanisms
  • Genomic instability
  • Telomere syndrome
  • Cancer

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مجله دانشکده پزشکی اصفهان
دوره 33، شماره 330 - شماره پیاپی 330
خرداد و تیر 1394
صفحه 522-535

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  • تاریخ دریافت: 12 آذر 1393
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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