Stability and function of RCL1 are dependent on the interaction with BMS1

During ribosome biogenesis,the small subunit(SSU)processome is responsible for 40S assembly.The BMS1/RCL1 complex is a core component of the SSU processome that plays an important role in 18S rRNA processing and maturation.Genetic studies using zebrafish mutants indicate that both Bms1-like(Bms1l)and Rcl1 are essential for digestive organ development.In spite of vital functions of this complex,the mutual dependence of these two nucleolar proteins for the stability and function remains elusive.In this study,we identified an RCL1-interacting domain in BMS1,which is conserved in zebrafish and humans.Moreover,both the protein stability and nucleolar entry of RCL1 depend on its interaction with BMS1,otherwise RCL1 degraded through the ubiquitination-proteasome pathway.Functional studies revealed that overexpression of RCL1 in BMS1-knockdown cells can partially rescue the defects in 18S rRNA processing and cell proliferation,and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1l^(sq163/sq163)but not in the knockout mutant bms1l^(zju1/zju1),which is attributed to the nucleolar entry of Rcl1 in the former mutant.Our data demonstrate that BMS1 and RCL1 interaction is essential for not only pre-rRNA processing but also the communication between ribosome biogenesis and cell cycle regulation.

Underestimated activity-based microplastic intake under scenariospecific exposures

Despite increasing alarms over the health impacts of microplastics(MPs)due to their detection in human organs and feces,precise exposure evaluations remain scarce.To comprehend their risks,there is a distinct need to prioritize quantitive estimates in MP exposome,particularly at the environmentallyrealistic level.Here we used a method rooted in real-world MP measurements and activity patterns to determine the daily intake of MPs through inhalation and from ground dust/soil ingestion.We found that nearly 80%of this intake comes from residential sectors,with activity intensity and behavioral types significantly affecting the human MP burden.The data showed a peak in MP exposure for those aged 18-64.When compared to dietary MP intake sources like seafood,salt,and water,we identified a previously underestimated exposure from inhalation and dust/soil ingestion,emphasizing the need for more realistic evaluations that incorporate activity factors.This discovery raises questions about the accuracy of past studies and underscores MP's potential health risks.Moreover,our time-based simulations revealed increased MP intake during the COVID-19 lockdown due to more surface dust ingestion,shedding light on how global health crises may inadvertently elevate MP exposure risks.

Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome

The cell cycle consists of four distinct phases:GO/Gl,S(DNA synthesis),G2,and M(mitosis).The Gl to S transition is typified by an accumulation of 4',6-diamidino-2-phenylindole(DAPI)signal that indicates the rapid DNA synthesis initiated at special sites on DNA,generally called the Ori(origin of replication)(Alfa et al.,1989).

Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication

18S,5.8S,and 28S ribosomal RNAs(rRNAs)are cotranscribed as a pre-ribosomal RNA(pre-rRNA)from the rDNA by RNA polymerase I whose activity is vigorous during the S-phase,leading to a conflict with rDNA replication.This conflict is resolved partly by replication-fork-barrier(RFB)-sites sequences located downstream of the rDNA and RFB-binding proteins such as Ttf1.However,how Ttf1 is displaced from RFB-sites to allow replication fork progression remains elusive.Here,we reported that loss-of-function of Bms1l,a nucleolar GTPase,upregulates rDNA transcription,causes replication-fork stall,and arrests cell cycle at the S-to-G2 transition;however,the G1-to-S transition is constitutively active characterized by persisting DNA synthesis.Concomitantly,ubf,tif-IA,and taf1b marking rDNA transcription,Chk2,Rad51,and p53 marking DNA-damage response,and Rpa2,PCNA,Fen1,and Ttf1 marking replication fork stall are all highly elevated in bms1l mutants.We found that Bms1 interacts with Ttf1 in addition to Rc1l.Finally,we identified RFB-sites for zebrafish Ttf1 through chromatin immunoprecipitation sequencing and showed that Bms1 disassociates the Ttf1–RFB complex with its GTPase activity.We propose that Bms1 functions to balance rDNA transcription and replication at the S-phase through interaction with Rcl1 and Ttf1,respectively.TTF1 and Bms1 together might impose an S-phase checkpoint at the rDNA loci.