Basal Splicing Factors Regulate the Stability of Mature mRNAs in Trypanosomes

Gupta, Sachin; Carmi, Shai; Ben‐Asher, Hiba Waldman; Tkacz, Itai Dov; Naboishchikov, Ilana; Michaeli, Shulamit

doi:10.1074/jbc.m112.416578

Cited by 43 publications

(59 citation statements)

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“…It is also possible that there are SL sequences modified by nucleotide changes at some sites, or completely different SL sequences ligated to the transcripts (Zhang et al, 2013). Finally, the biological role of the 5 0 leader sequence in vivo has not been clearly established, although it may play a role in either the regulation of translation or mRNA stability (Gupta et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions

et al. 2015

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SummarySymbiosis between unicellular dinoflagellates (genus Symbiodinium) and their cnidarian hosts (e.g. corals, sea anemones) is the foundation of coral reef ecosystems. Dysfunction of this symbiosis under changing environmental conditions has led to global reef decline. Little information is known about Symbiodinium gene expression and mechanisms by which light impacts host–symbiont associations. To address these issues, we generated a transcriptome from axenic Symbiodinium strain SSB01. Here we report features of the transcriptome, including occurrence and length distribution of spliced leader sequences, the functional landscape of encoded proteins and the impact of light on gene expression. Expression of many Symbiodinium genes appears to be significantly impacted by light. Transcript encoding cryptochrome 2 declined in high light while some transcripts for Regulators of Chromatin Condensation (RCC1) declined in the dark. We also identified a transcript encoding a light harvesting AcpPC protein with homology to Chlamydomonas LHCSR2. The level of this transcript increased in high light autotrophic conditions, suggesting that it is involved in photo‐protection and the dissipation of excess absorbed light energy. The most extensive changes in transcript abundances occurred when the algae were transferred from low light to darkness. Interestingly, transcripts encoding several cell adhesion proteins rapidly declined following movement of cultures to the dark, which correlated with a dramatic change in cell surface morphology, likely reflecting the complexity of the extracellular matrix. Thus, light‐sensitive cell adhesion proteins may play a role in establishing surface architecture, which may in turn alter interactions between the endosymbiont and its host.

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Section: Discussionmentioning

confidence: 99%

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions

et al. 2015

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“…Most recently, we demonstrated that the trypanosome homologs of these proteins not only function in splicing, but also in mRNA stabilization. 27 U2AF35 was also shown to bind to ribosomes and to associate with factors involved in rRNA processing and ribosome assembly. 27 Three SR proteins were identified in T. brucei, TSR1, TSR1IP, and RRM1.…”

Section: -13mentioning

confidence: 99%

“…27 U2AF35 was also shown to bind to ribosomes and to associate with factors involved in rRNA processing and ribosome assembly. 27 Three SR proteins were identified in T. brucei, TSR1, TSR1IP, and RRM1. [28][29][30] TSR1 contains an RS domain at its C terminus and two RRM domains at its N terminus.…”

Section: -13mentioning

confidence: 99%

“…Recently, we demonstrated that silencing basal splicing factors such as U2AF35 and SF1, increases the level of SL RNA; this is accompanied by a decrease in the level of Y structure intermediate, suggesting that these factors are essential for the first step of splicing. 27 An effect on the first step of splicing is evident by the decrease in the Y structure intermediate, whereas increase in the Y structure intermediate suggests effects on the second step of splicing. 33 Our results (Fig.…”

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Two splicing factors carrying serine-arginine motifs, TSR1 and TSR1IP, regulate splicing, mRNA stability, and rRNA processing inTrypanosoma brucei

Gupta¹,

Chikne²,

Eliaz³

et al. 2014

RNA Biology

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In trypanosomes, mRNas are processed by trans-splicing; in this process, a common exon, the spliced leader, is added to all mRNas from a small RNa donor, the spliced leader RNa (sL RNa). however, little is known regarding how this process is regulated. In this study, we investigated the function of two serine-arginine-rich proteins, TsR1 and TsR1IP, implicated in trans-splicing in Trypanosoma brucei. Depletion of these factors by RNai suggested their role in both cisand trans-splicing. Microarray was used to examine the transcriptome of the silenced cells. The level of hundreds of mRNas was changed, suggesting that these proteins have a role in regulating only a subset of T. brucei mRNas. Massspectrometry analyses of complexes associated with these proteins suggest that these factors function in mRNa stability, translation, and rRNa processing. We further demonstrate changes in the stability of mRNa as a result of depletion of the two TsR proteins. In addition, rRNa defects were observed under the depletion of U2aF35, TsR1, and TsR1IP, but not sF1, suggesting involvement of sR proteins in rRNa processing. ©2014 Landes Bioscience. Do not distribute 716RNa Biology Volume 11 Issue 6 among the hundreds of proteins present in the RNA polymerase II transcription complex, and are often loaded co-transcriptionally and accompany the fully spliced mRNA to the cytoplasm. 19 Since splice site consensus sequences are not sufficient to direct assembly of the spliceosome, sequences present in exons or introns such as exonic and intronic splicing enhancers (ESE and ISE), or exonic and intronic splicing silencers (ESS or ISS), are used to bind factors that regulate spliceosome assembly. SR proteins stabilize interactions between the U1 snRNP at the 5′ splice site and U2AF65 at the 3′ splice site. SR proteins are also known to bind to ESE and antagonize the activity of hnRNP proteins recognizing ESS. 20 In metazoa such as C. elegans, several SR proteins are essential, but others are not. 21 In mouse, many SR proteins are essential for life. 22 SR proteins have other functions in addition to their role in splicing, such as nuclear export, non-sense-mediated decay, and translation. SR proteins affect translation directly and indirectly. SF2/ASF was shown to associate with polyribosomes and to enhance translation, probably via release of 4E-BP, a competitive inhibitor of cap-dependent translation. 17 Recent studies support the role of SR proteins not only as splicing regulators, but also implicate these proteins in genome stability, chromatin binding, transcription elongation, mRNA stability, mRNA export, and translation (see review 23 ).The function of SR proteins is regulated by phosphorylation and de-phosphorylation. The RS domain is extensively phosphorylated on serine residues and this modification controls the localization of the protein. Mammalian SR proteins become dephosphorylated during the course of pre-mRNA processing, and promote mRNP transit through the nuclear pore complex. 24 SR proteins associate with the exon-junct...

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“…Two life cycle stages are routinely cultured in the laboratory: the bloodstream form, which is similar to the forms that multiply in mammalian blood and tissue fluids, and the procyclic form, which is similar to the parasites in the tsetse fly midgut. Different mRNA levels-and also regulation during differentiation-are achieved by modulation of mRNA decay (17) and trans-splicing (18)(19)(20). Trypanosome mRNA decay pathways are similar to those of other eukaryotes: mRNAs are deadenylated by a CAF1-NOT complex (21), then the mRNA body is attacked from the 3= end by the exosome (22)(23)(24) and in the 5=-3= direction by XRNA (25).…”

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confidence: 99%

Depletion of the Trypanosome Pumilio Domain Protein PUF2 or of Some Other Essential Proteins Causes Transcriptome Changes Related to Coding Region Length

et al. 2014

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Basal Splicing Factors Regulate the Stability of Mature mRNAs in Trypanosomes

Cited by 43 publications

References 74 publications

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions

Two splicing factors carrying serine-arginine motifs, TSR1 and TSR1IP, regulate splicing, mRNA stability, and rRNA processing inTrypanosoma brucei

Depletion of the Trypanosome Pumilio Domain Protein PUF2 or of Some Other Essential Proteins Causes Transcriptome Changes Related to Coding Region Length

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