Secondary structures in RNA synthesis, splicing and translation

Even though the functional role of mRNA molecules is primarily decided by the nucleotide sequence, several properties are determined by secondary structure conformations. Examples of secondary structures include long range interactions, hairpins, R-loops and G-quadruplexes and they are formed through interactions of non-adjacent nucleotides. Here, we discuss advances in our understanding of how secondary structures can impact RNA synthesis, splicing, translation and mRNA half-life. During RNA synthesis, secondary structures determine RNA polymerase II (RNAPII) speed, thereby influencing splicing. Splicing is also determined by RNA binding proteins and their binding rates are modulated by secondary structures. For the initiation of translation, secondary structures can control the choice of translation start site. Here, we highlight the mechanisms by which secondary structures modulate these processes, discuss advances in technologies to detect and study them systematically, and consider the roles of RNA secondary structures in disease.