The Function Of SON In RNA Pol ? Pausing Release Regulation

SON,formerly regarded as a DNA binding protein,is located in the nuclear speckles of eukaryotic nucleus.By recent study,SON has been found an important role as a scaffolding protein in maintaining proper nuclear organization of pre-mRNA processing factors in the nuclear speckles.Through the direct interaction with spliceosome components,SON plays a role in splicing.SON has also been found in the transcriptional regultion of specific genes that related to viral replication,pluripotency of stem cells,and acute leukemia,yet how does SON regulate the transcription that is completely elucidated.Depletion of SON in cells will result in the hyper-phosphorylation of RNA Pol ? at Ser2 which has been linked with the regultion of transcriptional elongation.All these studies implicate SON may have a role in transcriptional regulation.RNA Pol ? promoter-proximal pausing has been known as the key of transcription elongation regulation,and the release of Pol ? is largely depended on P-TEFb.Active P-TEFb is recruited to Pol ? and phosphorylates negative transcription factor DSIF and NELF and Pol ? CTD to release Pol II into elongation.SON is involved in multiple cellular processes,which is associated with cell cycle,cell growth,differentiation,virus infection and some diseases.In this study,we focus on the regulation of SON in transcription pausing-release of RNA Pol ?.By using HeLa cells as the cell model and HMBA treatment as Pol ? pausing release model,we verify RNA Pol ? phosphorylation is regulated by SON,and without SON,gene transcription can't upregulated even the signal pathway is activated.Then based on the techniques of modified nuclear fractionation,immunoprecipitation and ChIP,we find out that SON regulate partial P-TEFb recruitment pathway on Pol ?.With the absence of SON,Paflc will evicted from Pol ? and Pafl-SEC recruitment pathway is dissociated,SEC-P-TEFb can't be recruited to NELF-A for phosphorylation,then Pol? block in gene promoter region and can't turn into transcription elongation.This study reveals the role of nuclear speckles protein SON in transcription elongation regulation,laying a foundation for further exploring the relationship between nuclear speckles and transcription.