Insights into the RNA quadruplex binding specificity of DDX21

The Human RNA Helicase DDX21 Presents a Dimerization Interface Necessary for Helicase Activity

“…The flexibility of DDX21 may allow modulation of the accessibility of charged patches on its surface to bind certain protein or RNA partners. The C-terminal basic tail is essential for the recognition of this RNA structure ( Figure 4A), as shown by previous studies (McRae et al, , 2018. Further deletion of the GUCT domain strengthens the interaction to a moderate extent.…”

“…Still, an intact dimer interface is essential for maintaining this activity. In vitro experiments described by McRae et al ( , 2018 complement these findings as they show that the C-terminal domain of DDX21 can remodel G-quadruplexes in an ATP-independent manner. Their experiments used a construct covering the DD-GUCT and basic tail.…”

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

“…Our data underline the potential for the integration of rG4 therapeutics with an existing cancer treatment interest. Current research suggests that DDX21 has a unique specificity for certain rG4s that may be dependent on loop sequence 14,42 . Further work aims to identify the structure of the TV2 rG4 that DDX21 is recognizing, deciphering the specificity of DDX21 may potentially allow for the design of small molecules that specifically block its action.…”

“…UniprotKB. Search parameters were identical to as previously reported 42 . During data processing, the "Precursor Ion Area Detector" node of Proteome Discoverer 1.4.1.14's SEQUEST workflow editor was implemented to quantify the extracted ion chromatogram for each protein identified from the raw data.…”

“…Recently, we have shown that DDX21 can bind and unwind guanine-quadruplexes (rG4s) and affect the translation of a reporter construct with a rG4 in its 5' UTR 14 . This activity is mediated by an evolutionarily conserved region repeat region (F/PRGQR) in its C-terminus that preferentially interacts with the backbone of RNA rG4s 15 . It is unlikely that such an activity would exist and persist in an enzyme if there were no biological need for it.…”