SL RNA Biogenesis in Kinetoplastids: A Long and Winding Road

Sturm, Nancy R.; Zamudio, Jesse R.; Campbell, David A.

doi:10.1007/978-3-642-28687-2_2

Cited by 4 publications

(6 citation statements)

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“…Other proteins classified as essential (Alsford et al 2011) are found in the complexes, including the 117.5-kDa protein, which contains domains consistent with a role in RNA cap formation. Guanylyltransferase and N7-methyltransferase functions are required for the last two steps of eukaryotic mRNA cap formation (Ghosh and Lima 2010), however the enzyme identified here is distinct from that performing the nuclear co-transcriptional capping of the SL RNA, TbCGM1 (Ruan et al 2007;Takagi et al 2007; Sturm et al 2012). The further impact on distinct aspects of cell motility following knockdown of the TbE5 suggests unidentified roles for the complexes in the regulation of protein expression and function in these parasites.…”

Section: Discussionmentioning

confidence: 81%

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Freire

Vashisht

Malvezzi

et al. 2014

RNA

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Members of the eIF4E mRNA cap-binding family are involved in translation and the modulation of transcript availability in other systems as part of a three-component complex including eIF4G and eIF4A. The kinetoplastids possess four described eIF4E and five eIF4G homologs. We have identified two new eIF4E family proteins in Trypanosoma brucei, and define distinct complexes associated with the fifth member, TbEIF4E5. The cytosolic TbEIF4E5 protein binds cap 0 in vitro. TbEIF4E5 was found in association with two of the five TbEIF4Gs. TbIF4EG1 bound TbEIF4E5, a 47.5-kDa protein with two RNA-binding domains, and either the regulatory protein 14-3-3 II or a 117.5-kDa protein with guanylyltransferase and methyltransferase domains in a potentially dynamic interaction. The TbEIF4G2/TbEIF4E5 complex was associated with a 17.9-kDa hypothetical protein and both 14-3-3 variants I and II. Knockdown of TbEIF4E5 resulted in the loss of productive cell movement, as evidenced by the inability of the cells to remain in suspension in liquid culture and the loss of social motility on semisolid plating medium, as well as a minor reduction of translation. Cells appeared lethargic, as opposed to compromised in flagellar function per se. The minimal use of transcriptional control in kinetoplastids requires these organisms to implement downstream mechanisms to regulate gene expression, and the TbEIF4E5/TbEIF4G1/117.5-kDa complex in particular may be a key player in that process. We suggest that a pathway involved in cell motility is affected, directly or indirectly, by one of the TbEIF4E5 complexes.

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Section: Discussionmentioning

confidence: 81%

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Freire

Vashisht

Malvezzi

et al. 2014

RNA

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“…Unique to trypanosomatids, it also contains 2′-O methyl groups at nucleotides 3 and 4, and methylated bases at nucleotides 1 (m 2 6 A) and 4 (m 3 U) (Ullu and Tschudi, 1993). The functional significance of the trypanosomatid-specific hyper-methylated cap remains unclear (Sturm et al , 2012).…”

Section: Nuclear Gene Organization and Expressionmentioning

confidence: 99%

Recent advances in trypanosomatid research: genome organization, expression, metabolism, taxonomy and evolution

et al. 2018

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Unicellular flagellates of the family Trypanosomatidae are obligatory parasites of invertebrates, vertebrates and plants. Dixenous species are aetiological agents of a number of diseases in humans, domestic animals and plants. Their monoxenous relatives are restricted to insects. Because of the high biological diversity, adaptability to dramatically different environmental conditions, and omnipresence, these protists have major impact on all biotic communities that still needs to be fully elucidated. In addition, as these organisms represent a highly divergent evolutionary lineage, they are strikingly different from the common 'model system' eukaryotes, such as some mammals, plants or fungi. A number of excellent reviews, published over the past decade, were dedicated to specialized topics from the areas of trypanosomatid molecular and cell biology, biochemistry, host-parasite relationships or other aspects of these fascinating organisms. However, there is a need for a more comprehensive review that summarizing recent advances in the studies of trypanosomatids in the last 30 years, a task, which we tried to accomplish with the current paper.

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“…SL cap4 methylations at positions 1, 2 and 3/4 are carried out by the methyl transferases MTR1 (Zamudio et al ., ), MTR2 (also known as MT47 or COM1) (Arhin et al ., ; Hall and Ho, ) and MTR3 (also known as MT57) (Arhin et al ., ; Zamudio et al ., ) respectively, and they occur sequentially from position 1 to 4 (Mair et al ., ; recently reviewed by Sturm et al ., ). Previously, Tkacz et al .…”

Section: Resultsmentioning

confidence: 97%

“…SL cap4 methylations at positions 1, 2 and 3/4 are carried out by the methyl transferases MTR1 (Zamudio et al, 2007), MTR2 (also known as MT47 or COM1) (Arhin et al, 2006b;Hall and Ho, 2006) and MTR3 (also known as MT57) (Arhin et al, 2006a;Zamudio et al, 2006) respectively, and they occur sequentially from position 1 to 4 (Mair et al, 2000; recently reviewed by Sturm et al, 2012). Previously, Tkacz et al (2010) reported that The T. brucei PRP19 complex 893 PRP19 silencing led to a loss of cap3/4 and an accumulation of SL RNAs with cap2 indicating a functional link between PRP19 and MTR3.…”

Section: Spf27 Silencing Leads To Sl Cap Hypomethylationmentioning

confidence: 99%

The spliceosomal PRP19 complex of trypanosomes

Ambrósio

Badjatia

Günzl

2015

Molecular Microbiology

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Summary In trypanosomes, mRNAs are processed by spliced leader (SL) trans splicing, in which a capped SL, derived from SL RNA, is spliced onto the 5′ end of each mRNA. This process is mediated by the spliceosome, a large and dynamic RNA-protein machinery consisting of small nuclear ribonucleoproteins (snRNPs) and non-snRNP proteins. Due to early evolutionary divergence, the amino acid sequences of trypanosome splicing factors exhibit limited similarity to those of their eukaryotic orthologs making their bioinformatic identification challenging. Most of the ~ 60 protein components that have been characterized thus far are snRNP proteins because, in contrast to individual snRNPs, purification of intact spliceosomes has not been achieved yet. Here, we characterize the non-snRNP PRP19 complex of Trypanosoma brucei. We identified a complex that contained the core subunits PRP19, CDC5, PRL1, and SPF27, as well as PRP17, SKIP and PPIL1. Three of these proteins were newly annotated. The PRP19 complex was associated primarily with the activated spliceosome and, accordingly, SPF27 silencing blocked the first splicing step. Interestingly, SPF27 silencing caused an accumulation of SL RNA with a hypomethylated cap that closely resembled the defect observed previously upon depletion of the cyclin-dependent kinase CRK9, indicating that both proteins may function in spliceosome activation.

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SL RNA Biogenesis in Kinetoplastids: A Long and Winding Road

Cited by 4 publications

References 100 publications

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Recent advances in trypanosomatid research: genome organization, expression, metabolism, taxonomy and evolution

The spliceosomal PRP19 complex of trypanosomes

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