Characterizing RNA Pseudouridylation by Convolutional Neural Networks

Pseudouridine(Ψ)is the most prevalent post-transcriptional RNA modification and is widespread in small cellular RNAs and m RNAs.However,the functions,mechanisms,and precise distribution ofΨs(especially in m RNAs)still remain largely unclear.The landscape ofΨs across the transcriptome has not yet been fully delineated.Here,we present a highly effective model based on a convolutional neural network(CNN),called Pseudo Uridy Lation Site Estimator(PULSE),to analyze large-scale profiling data ofΨsites and characterize the contextual sequence features of pseudouridylation.PULSE,consisting of two alternatively-stacked convolution and pooling layers followed by a fully-connected neural network,can automatically learn the hidden patterns of pseudouridylation from the local sequence information.Extensive validation tests demonstrated that PULSE can outperform other state-of-the-art prediction methods and achieve high prediction accuracy,thus enabling us to further characterize the transcriptome-wide landscape ofΨsites.We further showed that the prediction results derived from PULSE can provide novel insights into understanding the functional roles of pseudouridylation,such as the regulations of RNA secondary structure,codon usage,translation,and RNA stability,and the connection to single nucleotide variants.The source code and final model for PULSE are available at https://github.com/mlcb-thu/PULSE.

SnoRNP is essential for thermospermine-mediated development in Arabidopsis thaliana

Polyamines have been discovered for hundreds of years and once considered as a class of phytohormones.Polyamines play critical roles in a range of developmental processes.However,the molecular mechanisms of polyamine signaling pathways remain poorly understood.Here,we measured the contents of main types of polyamines,and found that endogenous level of thermospermine(T-Spm)in Arabidopsis thaliana is comparable to those of classic phytohormones and is significantly lower than those of putrescine(Put),spermidine(Spd),and spermine(Spm).We further found a nodule-like structure around the junction area connecting the shoot and root of the T-Spm biosynthetic mutant acl5 and obtained more than 50 suppressors of acl5 nodule structure(san)through suppressor screening.An in-depth study of two san suppressors revealed that NAP57 and NOP56,core components of box H/ACA and C/D snoRNPs,were essential for T-Spm-mediated nodule-like structure formation and plant height.Furthermore,analyses of rRNA modifications showed that the overall levels of pseudouridylation and 2′-O-methylation were compromised in san1 and san2 respectively.Taken together,these results establish a strong genetic relationship between rRNA modification and T-Spm-mediated growth and development,which was previously undiscovered in all organisms.