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<p>From a historical perspective, long non-coding RNAs (lncRNAs) represent a relatively short story. However, this story has many plot lines, thrills, twists, and turns that altogether form quite a long saga of its own. lncRNAs stay at the forefront of a recent paradigm shift from a protein-only world to the mysterious RNA world, the enormous complexity of which we are only beginning to appreciate. Here, we review the most enigmatic aspect of lncRNAs, their coding ability in the context of whole-cell regulation. What peptides do lncRNAs encode as true translons? What is the mechanism of their translation? What roles do these ncRNA-encoded peptides (ncPEPs) play during differentiation and development and in distinct pathologies? Do these ncPEPs contribute to the already known regulatory roles of lncRNAs? Shouldn’t we coin the coding subset of lncRNAs its apt name: cryptic long non-coding RNAs (crpt-lncRNAs) for their cryptic coding capacity? These and other questions concerning these current winners of the spotlight in molecular biology, which await resolution, are discussed so that molecular history can be rewritten once again.</p>

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The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Leoš Shivaya Valášek,
  • Filip Brázdovič,
  • Filip Trčka,
  • Mahabub Pasha Mohammad,
  • Adriana Roithová

摘要

From a historical perspective, long non-coding RNAs (lncRNAs) represent a relatively short story. However, this story has many plot lines, thrills, twists, and turns that altogether form quite a long saga of its own. lncRNAs stay at the forefront of a recent paradigm shift from a protein-only world to the mysterious RNA world, the enormous complexity of which we are only beginning to appreciate. Here, we review the most enigmatic aspect of lncRNAs, their coding ability in the context of whole-cell regulation. What peptides do lncRNAs encode as true translons? What is the mechanism of their translation? What roles do these ncRNA-encoded peptides (ncPEPs) play during differentiation and development and in distinct pathologies? Do these ncPEPs contribute to the already known regulatory roles of lncRNAs? Shouldn’t we coin the coding subset of lncRNAs its apt name: cryptic long non-coding RNAs (crpt-lncRNAs) for their cryptic coding capacity? These and other questions concerning these current winners of the spotlight in molecular biology, which await resolution, are discussed so that molecular history can be rewritten once again.