Exploring the secrets of long noncoding RNAs

Abstract

High-throughput sequencing has revealed that the majority of RNAs have no capacity to encode protein. Among these non-coding transcripts, recent work has focused on the roles of long noncoding RNAs (lncRNAs) of >200 nucleotides. Although many of their attributes, such as patterns of expression, remain largely unknown, lncRNAs have key functions in transcriptional, post-transcriptional, and epigenetic gene regulation; Also, new work indicates their functions in scaffolding ribonuclear protein complexes. In plants, genome-wide identification of lncRNAs has been conducted in several species, including Zea mays, and recent research showed that lncRNAs regulate flowering time in the photoperiod pathway, and function in nodulation. In this review, we discuss the basic mechanisms by which lncRNAs regulate key cellular processes, using the large body of knowledge on animal and yeast lncRNAs to illustrate the significance of emerging work on lncRNAs in plants.

Figure 1

Four classes of lncRNAs. Blue indicates exons and white indicates introns; Black lines represent the coding and non-coding DNA strands. Red indicates lncRNAs, and arrows indicate the direction of transcription. Sense lncRNAs overlap with coding genes on the same strand. Antisense lncRNAs overlap with protein-coding genes on the opposite strand. Intronic lncRNAs occur completely within an intron. Intergenic lncRNAs occur between two genes.

Figure 2

Transcriptional regulation of lncRNAs. Red indicates lncRNAs, blue indicates protein-coding genes, pale blue indicates promoter areas, and green indicates proteins. (A) The transcription of SRG1 interferes with the expression of SER3; (B) The lncRNA HSR1 promotes the trimerization of HSF1 after heat shock. The HSF1 trimers bind to the HSR1 promoter and up-regulate HSR1 expression. The complex of HSF1 trimers, HSR1, and translation elongation factor eEF1A promotes the expression of HSPs; (C) NFAT is highly phosphorylated in the cytoplasm. Outside stimuli induce dephosphorylation of NFAT, which then moves into the nucleus to activate gene expression. NRON forms a complex with other proteins to prevent NFAT from moving into the nucleus, thus preventing the activation of the target gene.

Figure 3

The model of BACE1-AS lncRNAs. Black indicates BACE1 mRNA, red indicates BACE1-AS lncRNA, purple indicates miRNA, and orange and green circles indicate proteins. The BACE1-AS lncRNA can form perfect base pairs with the BACE1 mRNA for about 100 nucleotides, which includes the target site for miR-485-5p. The increased stability of BACE1 mRNA leads to increased abundance of BACE1 protein. BACE1 proteins proteolytically process the amyloid precursor protein into toxic substances such as β-amyloid peptides associated with Alzheimer’s disease.

Figure 4

The steps in initiation of X chromosome inactivation. The arrows (red, blue and purple) represent the transcriptional direction of lncRNAs. The solid arrows (red, blue and purple) indicate lncRNAs are expressed in corresponding loci, and the dotted arrows (red, blue and purple) with forks indicate the lncRNAs stop to transcribe in these loci. (A) Both Tsix and RepA recruit PRC2 to form a complex; Tsix prevents the RepA-PRC2 complex from loading onto chromatin; (B) Induction of JPX and loss of Tsix enable Xist expression; (C) RepA recruits PRC2 to the promoter of Xist; Xist co-transcriptionally recruits PRC2 to form a complex. YY1 binds with the complex in the nucleation center; (D) PRC2 binds to the chromatin and generates H3K27me3 (purple asterisks); (E) The Xist-PRC2 complex spreads along the chromosome from the nucleation center. PRC2 distributed on the chromosome generates H3K27me3.

Figure 5

LncRNAs from FLC. The blue bars indicate the exons of FLC sense transcripts. The arrows represent the direction of transcription. The red arrows indicate the direction of transcription. The red circular endpoints correspond to the 5' cap of lncRNAs. COLDAIR is transcribed from the first intron of FLC in the sense direction relative to FLC mRNA. COOLAIR and ASL transcripts are transcribed in the antisense direction. AS I and AS II, two antisense transcripts of COOLAIR, are transcribed in the antisense direction relative to FLC mRNA. Red boxes correspond to AS I and II exons, and dotted red lines correspond to the spliced regions of AS I and II. AS I has a proximal polyA in the sixth intron of FLC, and AS II has a distal polyA that overlaps with the promoter region of FLC. ASL is an antisense lncRNA with two isoforms produced by alternative spicing. The two red bold lines indicate the two isoforms of ASL. They transcribe from the same promoter as COOLAIR and span the first intron of FLC.