Characterization Of SPIN1 Nucleolar Localization And Function In RDNA Transcription

The interphase nucleolus is the most prominent structure in the cell nucleus where ribosomal RNAs(r RNA)are transcribed and processed,and ribosome subunits are assembled.The transcription of rDNA is the first and also rate-limiting step of ribosome biogenesis and is tightly regulated by the cellular physiology.Even a small change in the rDNA transcription may affect the cellular protein synthesis and further cell growth and division.SPIN1,identified as a member of Spin/Ssty family proteins,plays important roles in mouse oocyte development.Structural analysis revealed that SPIN1 contains three Tudorlike domains in tandem and possesses the ability to recognize histone methylation modifications.SPIN1 was reported to be highly expressed in many kinds of tumors.Consistently,overexpression of SPIN1 was shown to perturb cell cycle,induce chromosome instability and cause cell transformation.SPIN1 localizes in the nucleoli and facilitates r RNA gene expression.However,how SPIN1 localizes to the nucleolus and its functional role in r RNA gene expression remain unresolved.In the present study,we identified a nucleolar localization signal(NoLS)in the N-terminal region of SPIN1 that is essential for its enrichment and function in the nucleolus.We also discovered that,in addition to its H3K4me3 recognizing activity,the H3R8me2a-recognizing capacity of SPIN1 is also indispensable for stimulating r RNA expression,which is similar in SPIN1-promoted Wnt signaling.Using Ch IP experiments,we demonstrated that SPIN1 is required for the association or assembly of selectivity factor 1(SL1)complex,probably facilitating the initiation of rDNA transcription through its H3 “K4me3-R8me2a”methylation reader function.In conclusion,these results deepened our understanding of the role of SPIN1 in the nucleolus and further demonstrated the importance of SPIN1 in gene transcription as an epigenetic regulator.