REIIBP methylates nucleolar proteins and regulates pre-rRNA processing.

Area of Science:

• Molecular Biology
• Cell Biology
• Cancer Biology

Background:

• The NSD2 gene encodes a short isoform, REIIBP, which is overexpressed in t(4;14)+ multiple myeloma (MM).
• The biological functions of REIIBP have remained largely unknown.
• Understanding REIIBP's role is crucial for comprehending MM pathogenesis.

Purpose of the Study:

• To elucidate the biological functions of REIIBP.
• To investigate REIIBP's role in ribosome biogenesis and pre-ribosomal RNA (pre-rRNA) processing.
• To explore REIIBP's potential contribution to multiple myeloma.

Main Methods:

• Localization studies to determine REIIBP's cellular compartment.
• Analysis of REIIBP interactions with pre-ribosomal RNA (pre-rRNA).
• Proteomic analysis to identify associated proteins and post-translational modifications.
• Assessment of REIIBP's impact on pre-rRNA processing and ribosome biogenesis.

Main Results:

• REIIBP localizes to the dense fibrillar component (DFC) of the nucleolus.
• REIIBP's disordered regions bind to pre-rRNA, mediating its nucleolar localization.
• REIIBP associates with pre-rRNA processing factors and mediates their lysine methylation.
• REIIBP, via its disordered regions and SET domain, dysregulates pre-rRNA processing and ribosome biogenesis.

Conclusions:

• REIIBP plays a significant role in regulating ribosome biogenesis.
• REIIBP's dysregulation of pre-rRNA processing impacts cellular function.
• REIIBP may contribute to the pathological processes observed in multiple myeloma.