Ddx21, a member of the DEAD-box RNA helicase family, is pivotal in RNA metabolism, including ribosomal RNA (rRNA) processing, transcription, and translation. It is involved in diverse biological processes such as mRNA transcription, where it interacts with transcription factors, modulates RNA polymerase II elongation, binds R-loops, and participates in alternative splicing. It also has a role in ribosome biogenesis and genome stability, and its dysregulation is associated with cancer progression and potentially other diseases [4,5].

Glucose binds to the ATP-binding domain of Ddx21, altering its conformation, inhibiting helicase activity, and dissociating its dimers. This leads to Ddx21 re-localization during differentiation, promoting the splicing of pro-differentiation genes [1]. Ddx21 interacts with METTL3 for co-recruitment to chromatin via R-loops, facilitating m6A deposition on nascent RNA and transcription termination. Disrupting this process can induce DNA damage [2]. In colorectal cancer, phase-separated Ddx21 binds to the MCM5 gene locus, promoting metastasis through the EMT pathway [3].

In summary, Ddx21 has multifaceted functions in RNA metabolism and is involved in processes like tissue differentiation, transcription termination, and cancer metastasis. Studies on Ddx21, including those potentially using KO/CKO mouse models, help us understand its role in these biological processes and diseases, providing insights for potential biomarker and therapeutic target development [4,5].