RNA Group/Groupe ARN, Département de biochimie, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée au cancer, Université de Sherbrooke, QC J1E 4K8, Canada.
Nucleic Acids Res. 2014 Jan;42(2):1209-23. doi: 10.1093/nar/gkt904. Epub 2013 Oct 10.
G-quadruplexes (G4s) are non-canonical structures involved in many important cellular processes. To date, the prediction of potential G-quadruplex structures (PG4s) has been based almost exclusively on the sequence of interest agreeing with the algorithm Gx-N-1-7-Gx-N1-7-Gx-N1-7-Gx (where x ≥ 3 and N = A, U, G or C). However, many sequences agreeing with this algorithm do not form G4s and are considered false-positive predictions. Here we show the RNA PG4 candidate in the 3'-untranslated region (UTR) of the TTYH1 gene to be one such false positive. Specifically, G4 folding was observed to be inhibited by the presence of multiple-cytosine tracks, located in the candidate's genomic context, that adopted a Watson-Crick base-paired structure. Clearly, the neighbouring sequences of a PG4 may influence its folding. The secondary structure of 12 PG4 motifs along with either 15 or 50 nucleotides of their upstream and downstream genomic contexts were evaluated by in-line probing. Data permitted the development of a scoring system for the prediction of PG4s taking into account the effect of the neighbouring sequences. The accuracy of this scoring system was assessed by probing 14 other novel PG4 candidates retrieved in human 5'-UTRs. This new scoring system can be used, in combination with the standard algorithm, to better predict the folding of RNA G4s.
G-四链体（G4s）是参与许多重要细胞过程的非经典结构。迄今为止，潜在 G-四链体结构（PG4s）的预测几乎完全基于与算法 Gx-N-1-7-Gx-N1-7-Gx-N1-7-Gx（其中 x≥3 且 N=A、U、G 或 C）相吻合的感兴趣序列。然而，许多与该算法一致的序列并不形成 G4s，被认为是假阳性预测。在这里，我们展示 TTYH1 基因 3'-非翻译区（UTR）中的 RNA PG4 候选物就是这样一个假阳性。具体来说，观察到 G4 折叠受到位于候选物基因组背景中的多个胞嘧啶轨道的存在抑制，这些轨道采用沃森-克里克碱基配对结构。显然，PG4 的邻近序列可能会影响其折叠。通过在线探测评估了 12 个 PG4 基序的二级结构以及其上下游基因组背景的 15 或 50 个核苷酸。数据允许开发一种评分系统，用于预测 PG4s，同时考虑到邻近序列的影响。通过探测从人类 5'-UTR 中检索到的 14 个其他新的 PG4 候选物来评估该评分系统的准确性。该新的评分系统可以与标准算法结合使用，以更好地预测 RNA G4s 的折叠。
