The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei

Chikne, Vaibhav; Gupta, Sachin; Doniger, Tirza; Rajan, K. Shanmugha; Cohen-Chalamish, Smadar; Ben‐Asher, Hiba Waldman; Kolet, Liat; Hag-Yahia, Nasreen; Unger, Ron; Ullu, Elisabetta; Tschudi, Christian; Michaeli, Shulamit

doi:10.1016/j.jmb.2017.04.015

Cited by 17 publications

(11 citation statements)

References 73 publications

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“…Two genes encode potential poly(A) polymerases in T. brucei . One mRNA is cis spliced, and its product is implicated in small nucleolar RNA (snoRNA) processing [110]. The other, which has no intron, encodes the major mRNA poly(A) polymerase [111].…”

Section: Mrna Processing and Exportmentioning

confidence: 99%

Regulation of gene expression in trypanosomatids: living with polycistronic transcription

2019

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In trypanosomes, RNA polymerase II transcription is polycistronic and individual mRNAs are excised by trans -splicing and polyadenylation. The lack of individual gene transcription control is compensated by control of mRNA processing, translation and degradation. Although the basic mechanisms of mRNA decay and translation are evolutionarily conserved, there are also unique aspects, such as the existence of six cap-binding translation initiation factor homologues, a novel decapping enzyme and an mRNA stabilizing complex that is recruited by RNA-binding proteins. High-throughput analyses have identified nearly a hundred regulatory mRNA-binding proteins, making trypanosomes valuable as a model system to investigate post-transcriptional regulation.

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Section: Mrna Processing and Exportmentioning

confidence: 99%

Regulation of gene expression in trypanosomatids: living with polycistronic transcription

2019

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“…KKIP8 is one of 2 canonical poly(A) polymerases in trypanosomes, PAP1 and PAP2. PAP1 depletion has no detectable effect on mRNA polyadenylation, but causes an elevation of long non-coding RNA levels and precursors of small nucleolar RNAs (Chikne et al, 2017;Koch et al, 2016) KKIP12/RBP34 is a predicted RNA-binding protein that interacts with the trypanosomal homologue of Mkt1p in yeast 2-hybrid screens (Singh et al, 2014).…”

Section: New Components Suggest a Link Between Kinetochore Function Amentioning

confidence: 99%

Ndc80/Nuf2-like protein KKIP1 connects a stable kinetoplastid outer kinetochore complex to the inner kinetochore and responds to metaphase tension

Brusini¹,

D’Archivio²,

McDonald³

et al. 2019

Preprint

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Kinetochores perform an essential role in eukaryotes, coupling chromosomes to the mitotic spindle. In model organisms they are composed of a centromere-proximal inner kinetochore and an outer kinetochore network that binds to microtubules. In spite of its universal function, the composition of kinetochores in extant eukaryotes can differ greatly, and understanding how these different systems evolved and now function are important questions in cell biology. In trypanosomes and other Kinetoplastida, the kinetochores are extremely divergent, with most components showing no detectable similarity to proteins in other systems. They may also be very different functionally, potentially binding to the spindle directly via the inner kinetochore protein KKT4.However, we do not know the extent of the trypanosome kinetochore and proteins interacting with a highly divergent Ndc80/Nuf2-like protein, KKIP1, suggest the existence of more centromere-distal complexes. Here we use quantitative proteomics from multiple start-points to define a stable 9-protein kinetoplastid outer kinetochore (KOK) complex. Two of these core components were recruited from other nuclear processes, exemplifying the role of moonlighting proteins in kinetochore evolution. The complex is physically and biochemically distinct from KKT proteins, but KKIP1 links the inner and outer sets, with its C-terminus very close to the centromere and N-terminus at the outer kinetochore. Moreover, trypanosome kinetochores exhibit intrakinetochore movement during metaphase, primarily by elongation of KKIP1, consistent with pulling at the outer kinetochores. Together, these data suggest that the KOK complex, KKIP5 and N-terminus of KKIP1 likely constitute the extent of the trypanosome outer kinetochore and that this assembly binds to the spindle with sufficient strength to stretch the kinetochore.

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“…Virtually every protein-coding gene (∼8000) in T. brucei is transcribed from a small number (∼200) of multigene transcription units, with little evidence for functional grouping within the units (57). Only two genes have been described to have introns (58) and mature mRNAs are generated from multigene RNA transcripts by coupled trans -splicing and polyadenylation (59). Remarkably, some protein-coding genes in T. brucei are expressed from multigene units transcribed by RNA Pol I, where the promoters share some homology with those at rRNA gene clusters (60).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome

Briggs

Hamilton

Crouch

et al. 2018

Nucleic Acids Research

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R-loops are stable RNA–DNA hybrids that have been implicated in transcription initiation and termination, as well as in telomere maintenance, chromatin formation, and genome replication and instability. RNA Polymerase (Pol) II transcription in the protozoan parasite Trypanosoma brucei is highly unusual: virtually all genes are co-transcribed from multigene transcription units, with mRNAs generated by linked trans-splicing and polyadenylation, and transcription initiation sites display no conserved promoter motifs. Here, we describe the genome-wide distribution of R-loops in wild type mammal-infective T. brucei and in mutants lacking RNase H1, revealing both conserved and diverged functions. Conserved localization was found at centromeres, rRNA genes and retrotransposon-associated genes. RNA Pol II transcription initiation sites also displayed R-loops, suggesting a broadly conserved role despite the lack of promoter conservation or transcription initiation regulation. However, the most abundant sites of R-loop enrichment were within the regions between coding sequences of the multigene transcription units, where the hybrids coincide with sites of polyadenylation and nucleosome-depletion. Thus, instead of functioning in transcription termination the most widespread localization of R-loops in T. brucei suggests a novel correlation with pre-mRNA processing. Finally, we find little evidence for correlation between R-loop localization and mapped sites of DNA replication initiation.

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The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei

Cited by 17 publications

References 73 publications

Regulation of gene expression in trypanosomatids: living with polycistronic transcription

Regulation of gene expression in trypanosomatids: living with polycistronic transcription

Ndc80/Nuf2-like protein KKIP1 connects a stable kinetoplastid outer kinetochore complex to the inner kinetochore and responds to metaphase tension

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome

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