GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE85nnn/GSE85637/primaryOK2000000Genomics Trypanosoma bruceiTrypanosoma brucei brucei TREU927Expression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85637GEOGSE0falseTranscriptome and proteome analyses and the role of atypical calpain protein and autophagy in the spliced leader silencing pathway in Trypanosoma bruceiUnder persistent ER stress, Trypanosoma brucei parasites induce the spliced leader silencing (SLS) pathway. In SLS, transcription of the SL RNA gene, the SL donor to all mRNAs, is extinguished, arresting transsplicing and leading to programmed cell death(PCD). In this study, we investigated the transcriptome following silencing of SEC63, a factor essential for protein translocation across the ER membrane, and whose silencing induces SLS. The proteome of SEC63-silenced cells was analyzed with an emphasis on SLS-specific alterations in protein expression, and modifications that do not directly result from perturbations in trans-splicing. One such protein identified is an atypical calpain SKCRP7.1/7.2. Cosilencing of SKCRP7.1/7.2 and SEC63 eliminated SLS induction due its role in translocating the PK3 kinase. This kinase initiates SLS by migrating to the nucleus and phosphorylating TRF4 leading to shut-off of SL RNA transcription. Thus, SKCRP7.1 is involved in SLS signaling and the accompanying PCD. The role of autophagy in SLS was also investigated; eliminating autophagy through VPS34 or ATG7 silencing demonstrated that autophagy is not essential for SLS induction, but is associated with PCD. Thus, this study identified factors that are used by the parasite to cope with ER stress and to induce SLS and PCD.2017/08/01GSE85637GSM2280080GSM2280078GSM2280079GSM2280076GSM2280077GSM2280074GSM2280075GSM2280073223222232385637 Trypanosoma bruceiTrypanosoma brucei brucei TREU927[27161313]