Lasda Erika, Parker Roy
Department of Chemistry and Biochemistry & Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, United States of America.
PLoS One. 2016 Feb 5;11(2):e0148407. doi: 10.1371/journal.pone.0148407. eCollection 2016.
Backspliced circular RNAs (circRNAs) are prevalent in many eukaryotic systems and are spliced from thousands of different genes. Where examined, circRNAs are often highly stable and the mechanisms by which cells degrade and/or clear circRNAs from the cells are unknown. Here we investigated the possibility that cells can eliminate circRNAs into extracellular space, possibly within released vesicles such as exosomes and microvesicles. From three different cell lines and examining multiple circRNAs, we show that extracellular vesicle (EVs) preparations recovered from cell culture conditioned media contain established circRNAs. Moreover, these circRNAs are enriched over their linear counterparts within EV preparations when compared to the producing cells. This supports the idea that expulsion from cells into extracellular space, as by EVs release, can be a mechanism by which cells clear circRNAs. Moreover, since EVs can be taken up by other cells, excreted circRNAs could contribute to cell to cell communication.
反向剪接的环状RNA（circRNAs）在许多真核生物系统中普遍存在，且由数千个不同基因剪接而成。在已检测的情况下，circRNAs通常高度稳定，而细胞降解和/或清除细胞内circRNAs的机制尚不清楚。在此，我们研究了细胞是否能够将circRNAs释放到细胞外空间，可能是在诸如外泌体和微囊泡等释放的囊泡内。通过对三种不同细胞系进行检测并分析多种circRNAs，我们发现从细胞培养条件培养基中回收的细胞外囊泡（EVs）制剂中含有已确定的circRNAs。此外，与产生细胞相比，这些circRNAs在EV制剂中比其线性对应物更为富集。这支持了一种观点，即通过EVs释放从细胞排出到细胞外空间可能是细胞清除circRNAs的一种机制。此外，由于EVs可被其他细胞摄取，分泌的circRNAs可能有助于细胞间通讯。
