RNA plays essential roles in not only translating nucleic acids into proteins, but also in gene regulation, environmental interactions and many human diseases. Nature uses over 150 chemical modifications to decorate RNA and diversify its functions. With the fast-growing RNA research in the burgeoning field of ‘epitranscriptome’, a term describes post-transcriptional RNA modifications that can dynamically change the transcriptome, it becomes clear that these modifications participate in modulating gene expression and controlling the cell fate, thereby igniting the new interests in RNA based drug discovery. The dynamics of these RNA chemical modifications is orchestrated by coordinated actions of an array of writer, reader and eraser proteins. Deregulated expression of these RNA modifying proteins can lead to many human diseases including cancer. In this review, we highlight several critical modifications, namely m⁶A, m¹A, m⁵C, inosine and pseudouridine, in both coding and non-coding RNAs. In parallel, we present a few other cancer related tRNA and rRNA modifications. We further discuss their roles in cancer promotion or tumor suppression. Understanding the molecular mechanisms underlying the biogenesis and turnover of these RNA modifications will be of great significance in the design and development of novel anticancer drugs.

In this review, we highlight the importance of sulfur modifications in natural cellular RNAs and therapeutic nucleic acids. Sulfur modifications on RNA confer structural diversity, stability and enhance its functionality.

Cadmium (Cd) is one of the most toxic heavy metals. Exposure to Cd can impair the functions of the kidney, respiratory system, reproductive system and skeletal system. Cd²⁺-binding aptamers have been extensively utilized in the development of Cd²⁺-detecting devices; however, the underlying mechanisms remain elusive. This study reports four Cd²⁺-bound DNA aptamer structures, representing the only Cd²⁺-specific aptamer structures available to date. In all the structures, the Cd²⁺-binding loop (CBL-loop) adopts a compact, double-twisted conformation and the Cd²⁺ ion is mainly coordinated with the G9, C12 and G16 nucleotides. Moreover, T11 and A15 within the CBL-loop form one regular Watson–Crick pair and stabilize the conformation of G9. The conformation of G16 is stabilized by the G8–C18 pair of the stem. By folding and/or stabilizing the CBL-loop, the other four nucleotides of the CBL-loop also play important roles in Cd²⁺ binding. Similarly to the native sequence, crystal structures, circular dichroism spectrum and isothermal titration calorimetry analysis confirm that several variants of the aptamer can recognize Cd²⁺. This study not only reveals the underlying basis for the binding of Cd²⁺ ions with the aptamer, but also extends the sequence for the construction of novel metal–DNA complex.