Five alternative splicing variants of the TYR gene and their different roles in melanogenesis in the Muchuan black-boned chicken

The reactivation of telomerase in cancer cells remains incompletely understood. The catalytic component of telomerase, hTERT, is thought to be the limiting component in cancer cells for the formation of active enzymes. hTERT gene expression is regulated at several levels including chromatin, DNA methylation, transcription factors, and RNA processing events. Of these regulatory events, RNA processing has received little attention until recently. RNA processing and alternative splicing regulation have been explored to understand how hTERT is regulated in cancer cells. The cis- and trans-acting factors that regulate the alternative splicing choice of hTERT in the reverse transcriptase domain have been investigated. Further, it was discovered that the splicing factors that promote the production of full-length hTERT were also involved in cancer cell growth and survival. The goals are to review telomerase regulation via alternative splicing and the function of hTERT splicing variants and to point out how bioinformatics approaches are leading the way in elucidating the networks that regulate hTERT splicing choice and ultimately cancer growth.

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Two Alternative Splicing Variants of AtERF73/HRE1, HRE1α and HRE1β, Have Differential Transactivation Activities in Arabidopsis

International Journal of Molecular Sciences ◽

10.3390/ijms21196984 ◽

2020 ◽

Vol 21 (19) ◽

pp. 6984

Author(s):

Hye-Yeon Seok ◽

Jimin Ha ◽

Sun-Young Lee ◽

Hyoungjoon Bae ◽

Yong-Hwan Moon

Keyword(s):

Alternative Splicing ◽

Root Development ◽

Terminal Region ◽

Sequencing Analysis ◽

Regulate Gene Expression ◽

Hypoxia Response ◽

Transactivation Activity ◽

Gcc Box ◽

Splicing Variants ◽

Erf Transcription Factor

AtERF73/HRE1 is an AP2/ERF transcription factor in Arabidopsis and has two distinct alternative splicing variants, HRE1α and HRE1β. In this study, we examined the differences between the molecular functions of HRE1α and HRE1β. We found that HRE1α and HRE1β are both involved in hypoxia response and root development and have transactivation activity. Two conserved motifs in the C-terminal region of HRE1α and HRE1β, EELL and LWSY-like, contributed to their transactivation activity, specifically the four E residues in the EELL motif and the MGLWS amino acid sequence at the end of the LWSY-like motif. The N-terminal region of HRE1β also showed transactivation activity, mediated by the VDDG motif, whereas that of HRE1α did not. The transactivation activity of HRE1β was stronger than that of HRE1α in Arabidopsis protoplasts. Both transcription factors transactivated downstream genes via the GCC box. RNA-sequencing analysis further supported that both HRE1α and HRE1β might regulate gene expression associated with the hypoxia stress response, although they may transactivate different subsets of genes in downstream pathways. Our results, together with previous studies, suggested that HRE1α and HRE1β differentially transactivate downstream genes in hypoxia response and root development in Arabidopsis.

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