Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications

  • Cell Death Discov. 2024 Oct 23;10(1):450. doi: 10.1038/s41420-024-02175-0.
Yinan Xiao  #  1 ,  Yaru Ren  #  1 ,  Wenteng Hu  #  2 ,  Athanasios R Paliouras  3 ,  Wenyang Zhang  1 ,  Linghui Zhong  1 ,  Kaixin Yang  1 ,  Li Su  1 ,  Peng Wang  4 ,  Yonghong Li  5 ,  Minjie Ma  2 ,  Lei Shi  6
Affiliations
  • 1. RNA Oncology Group, School of Public Health, Lanzhou University, Lanzhou, 730000, PR China.
  • 2. Thoracic surgery department, The First Hospital, Lanzhou University, Lanzhou, 730000, PR China.
  • 3. Celeritas Insights 13, Freeland Park, Poole, BH16 6FA, UK.
  • 4. College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, PR China.
  • 5. NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, 730000, PR China.
  • 6. RNA Oncology Group, School of Public Health, Lanzhou University, Lanzhou, 730000, PR China. [email protected].
  • # Contributed equally.
Abstract

Long non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA Sequencing and ribosome nascent-chain complex Sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in Cancer.