Dudzik Jakub, Czechowicz Paulina, Więch-Walów Anna, Sławski Jakub, Collawn James F, Bartoszewski Rafal
Department of Biophysics, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wiley Interdiscip Rev RNA. 2025 Mar-Apr;16(2):e70012. doi: 10.1002/wrna.70012.
PIWI-interacting RNAs (piRNAs) are small non-coding RNA molecules that were originally described as responsible for binding to PIWI proteins to silence transposons in the germline genome. Here we discuss their controversial influence in regulating gene expression in human somatic cells. Although their functions in human somatic cells remain controversial, current research has focused on their potential contribution to human diseases including cancers and cardiovascular diseases (CVDs). These small RNA molecules directly interact with PIWI proteins to form piRNA-induced silencing complexes (piRISC). These complexes regulate not only long non-coding RNAs (lncRNAs) but also mRNAs in their 3' untranslated region. The controversy in human somatic cells occurs because not all of the reports demonstrate a direct interaction between the small non-coding RNAs and the PIWI proteins and also whether these established complexes have silencing activities. Therefore, their importance in human physiology and pathology continues to remain controversial. Here we discuss the challenges and limitations that need to be addressed in order to establish and harness the potential of these ncRNAs in potential clinical applications. In this review, we distinguish those examples that have been shown to function as silencing complexes (piRNAs) from those that appear to be silencing complexes based only on their ability to bind to PIWI proteins (piRNA-like) in human somatic cells.
PIWI相互作用RNA（piRNA）是一类小的非编码RNA分子，最初被描述为负责与PIWI蛋白结合，以使生殖系基因组中的转座子沉默。在此，我们讨论它们在调节人类体细胞基因表达方面存在争议的影响。尽管它们在人类体细胞中的功能仍存在争议，但目前的研究集中在它们对包括癌症和心血管疾病（CVD）在内的人类疾病的潜在作用。这些小RNA分子直接与PIWI蛋白相互作用，形成piRNA诱导沉默复合体（piRISC）。这些复合体不仅调节长链非编码RNA（lncRNA），还调节其3'非翻译区的mRNA。在人类体细胞中存在争议的原因是，并非所有报告都证明了小非编码RNA与PIWI蛋白之间的直接相互作用，以及这些已形成的复合体是否具有沉默活性。因此，它们在人类生理和病理中的重要性仍然存在争议。在此，我们讨论为了在潜在临床应用中建立和利用这些非编码RNA的潜力而需要解决的挑战和限制。在本综述中，我们区分了那些已被证明在人类体细胞中作为沉默复合体发挥作用的例子（piRNA）和那些仅基于其与PIWI蛋白结合能力而看似沉默复合体的例子（类piRNA）。
