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Downstream-of-Gene Transcript Research

DoG RNAs Modulate Gene Transcription in Diseases

 

The functional roles of read-through transcription and DoG RNAs are currently the focus of active research, with several proposed mechanisms highlighting their involvement in gene regulation.

DoG RNAs mediate transcriptional interference in cell senescence

DoGs can act as antisense RNAs to control the gene expression of convergent protein-coding genes. In senescent cells, a family of senescence-triggered antisense read-through RNAs (START RNAs) are induced as DoGs[1]. Importantly, START RNAs repress the expression of their corresponding sense RNAs.

Another example is SVK located in a cold-sensitive region of Arabidopsis genome. RNAPII read-through transcription of SVK results in a cryptic lncRNA- asCBF1 overlapping CBF1 on the antisense strand[2]. CBF1 is suppressed by RNAPII collision stemming from the SVK-asCBF1 lncRNA cascade (Fig. 1). The SVK-asCBF1 cascade provides a mechanism to tightly control CBF1 expression and timing upon cold stress.

Modulate_Gene_Transcription-1

Figure 1. Control of CBF1 coding gene expression by antisense DoG RNA. (Left) At normal temperature, CBF1 can be transcribed without hindrance. (Right) Upon cold exposure, SVK transcription is increased in the antisense direction of CBF1. SVK read-through transcription results in transcription antisense to the 3′-end of CBF1. The increased occupancy of transcribing RNAPII on both strands creates RNAPII collision and stalling of CBF1 sense transcription, causing reduced full-length CBF1 mRNA production[2].

DoG RNA regulates Genome 3D organization in viral infection

During influenza A virus (IAV) infection, viral nonstructural protein NS1 induces read-through transcription of highly active host genes, causing displacement of cohesin from the host chromatin, elimination of chromatin loops, and decompaction of chromatin in the read-through regions (Fig. 2)[3].

Modulate_Gene_Transcription-3

Figure 2. Read-through transcription alters chromatin structure. Influenza A virus (IAV) protein NS1 disrupts transcription termination, allowing RNAPII to proceed past the termination sites and leading to a loss of chromatin loops and local chromatin decompaction [3].

 

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References
1.  Muniz L et al: Control of Gene Expression in Senescence through Transcriptional Read-Through of Convergent Protein-Coding Genes. Cell Rep 2017, 21(9):2433-2446.[PMID: 29186682]
2.  Kindgren P, Ard R, Ivanov M, Marquardt S: Transcriptional read-through of the long non-coding RNA SVALKA governs plant cold acclimation. Nat Commun 2018, 9(1):4561.[PMID: 30385760]
3.  Heinz S et al: Transcription Elongation Can Affect Genome 3D Structure. Cell 2018, 174(6):1522-1536 e1522.[PMID: 30146161]

 

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