DDX27

DDX27 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis through its association with the rRNA processing machinery (PMID:25825154, PMID:29518074). It stably binds the PeBoW-complex (Pes1, Bop1, WDR12) via a conserved F×F motif in its N-terminal domain, while its basic C-terminal domain mediates RNA-dependent recruitment to the nucleolus independently of PeBoW (PMID:25825154). DDX27 is required for proper 3' end formation of the primary 47S pre-rRNA, a function it carries out independently of the PeBoW-complex, since its loss causes accumulation of an extended 47S species (PMID:25825154). Through control of rRNA maturation and ribosome biogenesis, DDX27 governs the translation of specific transcripts during myogenesis, and its loss impairs skeletal muscle growth and regeneration in vivo (PMID:29518074). Beyond ribosome biogenesis, DDX27 participates in cancer-associated RNA processing and gene regulation: it interacts with SRSF6 to direct alternative splicing of BRD4 pre-mRNA toward the BRD4-S isoform and activate MAPK/ERK signaling (PMID:41198561), promotes oral squamous carcinoma growth through the downstream effector CSE1L (PMID:38301874), and drives colorectal cancer progression in part by transcriptional upregulation of EZH2 (PMID:41045764).

1. 2015 High

   Established how DDX27 is anchored within the nucleolar ribosome biogenesis machinery, defining the molecular basis of its recruitment and its complex membership.

   Evidence Mass spectrometry, reciprocal Co-IP, and domain mapping with F×F motif mutagenesis in human cells

   PMID:25825154

   Open questions at the time

   • Helicase catalytic activity on rRNA not directly demonstrated
   • Functional consequence of PeBoW association versus independent nucleolar recruitment not separated
2. 2015 Medium

   Assigned DDX27 a specific, PeBoW-independent step in pre-rRNA processing by showing it is required for correct 47S 3' end formation.

   Evidence siRNA knockdown of DDX27 versus Pes1 with Northern/rRNA processing analysis

   PMID:25825154

   Open questions at the time

   • Direct enzymatic mechanism of 3' end maturation not resolved
   • Single method (rRNA analysis) from one lab
3. 2018 High

   Connected DDX27's rRNA maturation function to an in vivo physiological process, showing ribosome biogenesis through DDX27 is required for skeletal muscle growth and regeneration.

   Evidence Genetic screen and zebrafish loss-of-function with rRNA maturation and translational profiling readouts

   PMID:29518074

   Open questions at the time

   • Mechanism linking specific transcript translation to muscle phenotype not fully defined
   • Direct rRNA substrate engagement not shown in vivo
4. 2024 Medium

   Extended DDX27 function to tumor growth by identifying CSE1L as a physical partner and required downstream effector in oral squamous cell carcinoma.

   Evidence Co-IP, shRNA knockdown, rescue experiments, and xenograft models

   PMID:38301874

   Open questions at the time

   • Single Co-IP without reciprocal validation
   • Mechanism by which DDX27 controls CSE1L unknown
5. 2025 Medium

   Defined a splicing-regulatory role for DDX27, showing it cooperates with SRSF6 to bias BRD4 splicing toward BRD4-S and activate MAPK/ERK signaling in colorectal cancer.

   Evidence Co-IP, RNA-IP, splicing assays, SRSF6 phosphorylation inhibition, and xenograft

   PMID:41198561

   Open questions at the time

   • Direct binding of DDX27 to BRD4 pre-mRNA versus indirect via SRSF6 not fully separated
   • Single lab
6. 2025 Medium

   Implicated DDX27 in transcriptional control by linking it to upregulation of EZH2 during colorectal cancer progression.

   Evidence siRNA knockdown, EZH2 promoter luciferase reporter, RNA-seq, Western blot, and xenograft

   PMID:41045764

   Open questions at the time

   • Mechanism by which a nucleolar helicase affects EZH2 promoter activity unresolved
   • Direct versus indirect transcriptional effect not distinguished

• Whether DDX27's nucleolar rRNA-processing activity mechanistically underlies its disparate cancer-associated splicing, transcriptional, and protein-partner functions remains unresolved.
• No unifying mechanism connecting ribosome biogenesis to splicing/transcriptional roles
• Direct RNA helicase activity not biochemically reconstituted
• Substrate specificity of the helicase domain uncharacterized