Fig 1.
Graphical representation of different types of lncRNAs identified in P. falciparum.
(A) Intronic lncRNAs, transcribed from the intronic region of protein-coding genes. (B) lincRNA, located between 2 protein-coding genes. (C) Antisense lncRNAs, transcribed from the antisense strand of protein-coding genes. (D) Bidirectional lncRNA, transcribed from the opposite strand by a bidirectional promoter, and (E) circRNAs generated through back-splicing of transcripts with intronic, exonic or intronic and exonic fragments. (F) Putative lncRNA identified in P. falciparum using PacBio and Illumina sequencing [27,35]. Both studies reported a relatively large number of differentially expressed lncRNAs during intra erythrocytic development. circRNA, circular RNA; lncRNA, long ncRNA; lincRNA, long intergenic lncRNA.
Table 1.
Various sequencing techniques used to study ncRNAs in P. falciparum.
Fig 2.
Functionally characterized lncRNAs in P. falciparum.
(A) lncRNAs involved in mutually exclusive expression of var genes. Schematic representation of a var gene locus composed of a variable exon 1, bidirectional promoter within the intron, and a conserved exon 2. The upstream var promoter engages in the transcription of the mRNA, while the intronic bidirectional promoter is involved in the production of sense and antisense lncRNA transcripts. The silent var gene transcribes sense ncRNA from the promoter within the intron (left). In the active state of the var gene, RNA polymerase II transcribes both an mRNA in the sense direction and an lncRNA in the antisense direction (right). (B) Intergenic GC-rich ncRNAs transcribed from internal var chromosomal clusters in P. falciparum. These GC-rich ncRNAs are predicted to be transcribed by RNA polymerase III. (C) Schematic representation of P. falciparum telomere and TAREs and subtelomeric gene families. (D) lncRNA’s involvement in sexual commitment. Sexual commitment in Plasmodium is regulated by GDV1, whose expression is antagonistically regulated by its antisense lncRNA. Once expressed, GDV1 reverses HP1-dependent silencing of AP2-G and inhibits sexual commitment. GDV1, gametocyte development 1; HP1, heterochromatin protein 1; lncRNA, long ncRNA; ncRNA, noncoding RNA; TARE, telomere-associated repeat.
Fig 3.
lncRNAs operate by different mechanisms.
The subcellular localization of lncRNAs determines their mechanisms and biological functions. Inside the nucleus (upper) they can perform regulatory functions such as (A) scaffolds for recruitment of regulatory factors and protein complexes, (B) regulation of chromatin conformation/chromatin architecture, (C) transcription regulation of target genes, and (D) regulation of pre-mRNA splicing. Cytoplasmic lncRNAs (lower) are involved in the modulation of (E) mRNA stability and decay, (F) mRNA translation, and act as a (G) miRNA sponge to inhibit host (human)-encoded miRNAs. circRNA, circular RNA; lncRNA, long ncRNA; miRNA, microRNA.
Fig 4.
Splicing and translation of lncRNAs.
(A) P. falciparum lncRNAs can undergo AS (left panel) and generate circRNAs as demonstrated for ARP_circRNA (apoptosis related protein circRNA) (right panel). (B) Some lncRNAs contain sORFs that are translated into small proteins with different biological roles, such as transcriptional and translational regulation, mRNA splicing, signal transduction, mitochondrial regulation, calcium transport, and lysosomal degradation. AS, alternative splicing; circRNA, circular RNA; lncRNA, long ncRNA; sORF, small open reading frame.