Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

Chakrabarti, Kausik; Pearson, Michael; Grate, Leslie R.; Sterne-Weiler, Timothy; Deans, Jonathan; Donohue, John P.; Ares, Manuel

doi:10.1261/rna.751807

Cited by 93 publications

(120 citation statements)

References 131 publications

(159 reference statements)

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“…The combined Northern and microarray analyses presented here extend the repertoire of novel ncRNA transcripts to a total of 33, transcribed within asexual stages of the life cycle. Twenty-nine of our candidates overlap structured ncRNAs (three previously known snRNAs, four of our "candidate" RNAs, and 22 of our "selected" RNAs) described recently by Chakrabarti et al (2007). Interestingly, this study has provided independent evidence for the expression of the chromosomeinternal, var gene-associated, novel structured ncRNA family in P. falciparum described previously.…”

Section: Discussionsupporting

confidence: 59%

“…Transcripts were detected in asexual parasites' RNA for six of the 18 candidates, but only one of these six was a novel RNA. Recently, a more elaborate study, using comparative genomics and RNA analysis, has identified several components of the structured RNAs of known function (i.e., spliceosomal and small nucleolar RNAs, telomerase RNA) and a small number of structured RNAs of unknown function in P. falciparum (Chakrabarti et al 2007). …”

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confidence: 99%

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Genome-wide discovery and verification of novel structured RNAs inPlasmodium falciparum

et al. 2007

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We undertook a genome-wide search for novel noncoding RNAs (ncRNA) in the malaria parasite Plasmodium falciparum. We used the RNAz program to predict structures in the noncoding regions of the P. falciparum 3D7 genome that were conserved with at least one of seven other Plasmodium spp. genome sequences. By using Northern blot analysis for 76 high-scoring predictions and microarray analysis for the majority of candidates, we have verified the expression of 33 novel ncRNA transcripts including four members of a ncRNA family in the asexual blood stage. These transcripts represent novel structured ncRNAs in P. falciparum and are not represented in any RNA databases. We provide supporting evidence for purifying selection acting on the experimentally verified ncRNAs by comparing the nucleotide substitutions in the predicted ncRNA candidate structures in P. falciparum with the closely related chimp malaria parasite P. reichenowi. The high confirmation rate within a single parasite life cycle stage suggests that many more of the predictions may be expressed in other stages of the organism's life cycle.

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Section: Discussionsupporting

confidence: 59%

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confidence: 99%

Genome-wide discovery and verification of novel structured RNAs inPlasmodium falciparum

et al. 2007

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“…In much the same way, sterile transcripts may direct chromatin-associated factors to target specific var genes for silencing. Given the data presented here, the recent identification in silico of more than 30 novel ncRNAs of unknown function (Chakrabarti et al 2007;Mourier et al 2008) and evidence that 17% of annotated var noncoding RNAs www.rnajournal.org 123 genes express detectable antisense RNA transcripts, it is likely that RNA-mediated gene regulation is an integral part of P. falciparum biology (Patankar et al 2001).…”

Section: Discussionmentioning

confidence: 87%

Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum

Epp¹,

Li²,

Howitt³

et al. 2008

RNA

123

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Antigenic variation by the malaria parasite Plasmodium falciparum results from switches in expression between members of the multicopy var gene family. These genes encode the variant surface protein PfEMP-1, the primary determinant of the antigenic and cytoadherent properties of infected erythrocytes. Only a single var gene is expressed at a time while the remaining members of the family remain transcriptionally silent. How mutually exclusive var gene expression is regulated is poorly understood; however, it is generally thought to involve alterations in chromatin assembly and modification, resulting in a type of cellular memory. Recently, several aspects of the chromatin structure surrounding var genes have been described, in particular the histone modifications associated with the active and silent states of the genes as well as their subnuclear localization. Here, we demonstrate that this chromatin structure also includes the incorporation of long sense and antisense noncoding RNAs. These sterile transcripts initiate from a bidirectional promoter located within a conserved intron found in all var genes that was previously implicated in var gene silencing. Mapping of the 59 and 39 ends of the sterile transcripts indicates that they are nonpolyadenylated. RNA fluorescent in situ hybridization (RNA-FISH) analysis detects both the sense and antisense noncoding RNAs in distinct spots within the nucleus similar to the pattern described for the var genes themselves. Further, analysis by RNA chromatin immunoprecipitation (ChIP) indicates that the noncoding RNAs are physically associated with chromatin. These sterile transcripts therefore might act in a manner analogous to noncoding RNAs associated with silent, condensed chromatin found in other eukaryotic systems.

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“…Derivation of separate secondary structure models for telomerase RNAs from ciliates, vertebrates, and budding yeasts have revealed several conserved motifs, which include a single-stranded region encompassing the template and a pseudoknot present in a central core domain as well as a 39 stem-terminus element (Theimer and Feigon 2006). However, telomerase RNAs display an exceptional degree of evolutionary diversity, with a striking degree of length variation (ranging from 147 nt to >2 kb) (Ye and Romero 2002;Chakrabarti et al 2007;Kachouri-Lafond et al 2009) which is accompanied by sequence divergence even within the conserved structural motifs. The tolerance to such a high degree of variation might be explained if the RNA subunit does not fold into a compact well-defined threedimensional structure with fixed orientation of structural elements.…”

Section: Introductionmentioning

confidence: 99%

The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements

Lubin

Tucey

Lundblad

2012

RNA

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In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Previous work has identified a conserved 5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1 to TLC1. However, increased expression of Est1 can bypass the consequences of removal of this RNA bulge, indicating that there are additional binding site(s) for Est1 on TLC1. We report here that a conserved single-stranded internal loop immediately adjacent to the bulge is also required for the Est1-RNA interaction; furthermore, a TLC1 variant that lacks this internal loop but retains the bulge cannot be suppressed by Est1 overexpression, arguing that the internal loop may be a more critical element for Est1 binding. An additional structural feature consisting of a single-stranded region at the base of the helix containing the bulge and internal loop also contributes to recognition of TLC1 by Est1, potentially by providing flexibility to this helical arm. Association of Est1 with each of these TLC1 motifs was assessed using a highly sensitive biochemical assay that simultaneously monitors the relative levels of the Est1 and Est2 proteins in the telomerase complex. The identification of three elements of TLC1 that are required for Est1 association provides a detailed view of this particular protein-RNA interaction.

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Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

Cited by 93 publications

References 131 publications

Genome-wide discovery and verification of novel structured RNAs inPlasmodium falciparum

Genome-wide discovery and verification of novel structured RNAs inPlasmodium falciparum

Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum

The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements

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