Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates

Wilson, Kitchener D.; Ameen, Mohamed; Guo, Hongchao; Abilez, Oscar J.; Tian, Lei; Mumbach, Maxwell R.; Diecke, Sebastian; Qin, Xulei; Liu, Yonggang; Yang, Huaxiao; Ma, Ning; Gaddam, Sadhana; Cunningham, Nathan J.; Gu, Mingxia; Neofytou, Evgenios; Prado, Maricela; Hildebrandt, Thomas B.; Karakikes, Ioannis; Chang, Howard Y.; Wu, Joseph C.

doi:10.1016/j.devcel.2020.07.006

Cited by 46 publications

(36 citation statements)

References 62 publications

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“…Some ERV-derived RNAs also function as long non-coding RNAs (lncRNAs). Recent studies have reported that ERV-derived lncRNAs can affect the host gene regulatory networks by binding to host RNA binding proteins (49, 50, 51). Such lncRNAs may harbor RNA elements that have evolved to provide advantages to ancient retroviruses.…”

Section: Discussionmentioning

confidence: 99%

An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation

Kitao

Nakagawa

Miyazawa

2021

Preprint

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Retroviruses utilize multiple unique RNA elements to control several aspects of RNA processing, such as splicing, subcellular export, and translation. However, it is mostly unclear whether such functional RNA elements are present in endogenous retroviruses (ERVs), many of which were inserted into the host genomes millions of years ago. Previously, in human ERV-derived syncytin-1 gene, we found a cis-acting RNA element named SPRE that enhances its protein expression. In this study, we found a 17-nt common sequence in SPRE of syncytin-1 and another ERV-derived gene, syncytin-2, and the sequence is confirmed to be essential for the expression of the proteins. We detected the sequences of SPRE-like elements in 41 ERV families. Though the SPRE-like elements were not found in currently prevailing (i.e. exogenous) viral sequences, more than thousands of copies of the elements were found in several mammalian genomes, suggesting the ancient integration and propagation of the SPRE-harboring retroviruses in mammalian lineages. Indeed, other mammalian ERV-derived genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora contain the SPRE-like elements, and we validated their function for efficient protein expression by in vitro assays. A reporter assay revealed that the enhancement of gene expression by SPRE depended on reporter genes. Moreover, the mutation in SPRE did not affect the gene expression in codon-optimized syncytin-2. However, the same mutation in SPRE impaired the gene expression in wild-type syncytin-2, suggesting that the SPRE dependency of Syncytin-2 expression is due to the negative factors such as inefficient codon frequency or repressive elements within the coding sequence. These results provide new implications that ERVs harbor unique RNA elements involved in the regulation of ERV-derived genes.

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Section: Discussionmentioning

confidence: 99%

An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation

Kitao

Nakagawa

Miyazawa

2021

Preprint

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“…More recently, Wilson et al (2020) described BANCR, a lncRNA exclusively expressed in primate fetal cardiomyocytes. BANCR promotes cardiomyocyte migration in vitro and ventricular enlargement in vivo .…”

Section: A Role For Lncrnas In Heart Regenerationmentioning

confidence: 99%

“…Additionally, the authors identified TEAD4 and YAP1 (two factors involved in the HIPPO pathway) in the same enhancer, promoting BANCR expression. Finally, the authors identified a role for BANCR in heart disease, demonstrating higher expression in pediatric but not adult dilated cardiomyopathy ( Nelakanti and Xiao, 2020 ; Wilson et al, 2020 ). Other lncRNAs associated with aged hearts include lncRNA H19 (downregulated in aged or ischemic heart; Hofmann et al, 2019 ), and MALAT1 a lncRNA which, itself, is regulated by an antisense lncRNA transcript (TALAM1; Zong et al, 2016 ; Gomes et al, 2019 ), was also shown to be decreased in aged hearts ( Bink et al, 2019 ; Gomes et al, 2019 ), and this decrease was shown to be involved in cardiac dysfunction ( Zhu et al, 2019 ; Li et al, 2020a ).…”

Section: A Role For Lncrnas In Heart Regenerationmentioning

confidence: 99%

Age-Related Pathways in Cardiac Regeneration: A Role for lncRNAs?

et al. 2021

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Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangement of the cardiac structure and function and to a subsequent increased risk of heart failure. An intricate network of distinct pathways contributes to age-related alterations during healthy heart aging and account for a higher susceptibility of heart disease. Our understanding of the systemic aging process has already led to the design of anti-aging strategies or to the adoption of protective interventions. Nevertheless, our understanding of the molecular determinants operating during cardiac aging or repair remains limited. Here, we will summarize the molecular and physiological alterations that occur during aging of the heart, highlighting the potential role for long non-coding RNAs (lncRNAs) as novel and valuable targets in cardiac regeneration/repair.

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“…24 In addition, the endogenous retrovirus-derived lncRNA BANCR is exclusively expressed in fetal cardiomyocytes and promotes the cardiac differentiation and maturation of human and nonhuman primate PSCs. 25 The human-specific lncRNA HBL1 was identified through a transcriptome analysis of ESCs undergoing cardiomyocyte differentiation. The overexpression of HBL1 inhibits and loss-of-function of HBL1 promotes cardiomyocyte differentiation from iPSCs.…”

Section: Biological Function Of Lncrnas In the Early Differentiatiomentioning

confidence: 99%

Lnc‐ing pluripotency maintenance and early differentiation in human pluripotent stem cells

Zhang

et al. 2021

The FASEB Journal

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Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self-renewal or differentiation is under the exquisite control of the gene regulatory network, which is composed of transcription factors, signaling pathways, metabolic factors, chromatin or histone modifiers, miRNAs, and lncRNAs. Growing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in epigenetic, transcriptional, and posttranscriptional gene regulation during the cell fate determination of pluripotent stem cells. Here, we summarize recent reports of lncRNA functions in pluripotency maintenance/exit and the early germ layer specification of human pluripotent stem cells. We also illustrate four major lncRNA functional mechanisms according to different types of cofactors: chromatin or histone modifiers, transcription factors, canonical and noncanonical RNA-binding proteins, and miRNAs. Further understanding of lncRNA-based regulation will provide more insights into the drivers manipulating cell fate and promote the therapeutic and research potential of human embryonic and induced pluripotent stem cells.

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Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates

Cited by 46 publications

References 62 publications

An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation

An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation

Age-Related Pathways in Cardiac Regeneration: A Role for lncRNAs?

Lnc‐ing pluripotency maintenance and early differentiation in human pluripotent stem cells

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