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LARP1亚型在人类癌细胞系中的表达。

LARP1 isoform expression in human cancer cell lines.

作者信息

Schwenzer Hagen, Abdel Mouti Mai, Neubert Pia, Morris Josephine, Stockton Joanne, Bonham Sarah, Fellermeyer Martin, Chettle James, Fischer Roman, Beggs Andrew D, Blagden Sarah P

机构信息

Department of Oncology, University of Oxford, Oxford, UK.

Institute of Cancer & Genomic Sciences, University of Birmingham, Birmingham, UK.

出版信息

RNA Biol. 2021 Feb;18(2):237-247. doi: 10.1080/15476286.2020.1744320. Epub 2020 Apr 14.

Abstract

LARP1 is an oncogenic RNA-binding protein required for ribosome biogenesis and cancer cell survival. From published studies, there is disparity over which of two different LARP1 protein isoforms (termed the long LI-LARP1 and short SI-LARP1) is the canonical. Here, after conducting a series of biochemical and cellular assays, we conclude that LI-LARP1 (NM_033551.3 > NP_056130.2) is the dominantly expressed form. We observe that SI-LARP1 (NM_015315.5> NP_056130.2) is epigenetically repressed and that this repression is evolutionarily conserved in all but a small subclade of mammalian species. As with other LARP family members, there are multiple potential LARP1 mRNA isoforms that appear to be censored within the nucleus. The capacity of the cell to modulate splicing and expression of these apparently 'redundant' mRNAs hints at contextually specific mechanisms of LARP1 expression.

摘要

LARP1是一种核糖体生物合成和癌细胞存活所必需的致癌性RNA结合蛋白。从已发表的研究来看,两种不同的LARP1蛋白异构体(分别称为长链LI-LARP1和短链SI-LARP1)哪一种是标准型存在差异。在此,在进行了一系列生化和细胞分析后,我们得出结论,LI-LARP1(NM_033551.3>NP_056130.2)是主要表达形式。我们观察到SI-LARP1(NM_015315.5>NP_056130.2)在表观遗传上受到抑制,并且除了一小部分哺乳动物亚分支外,这种抑制在所有物种中都是进化保守的。与其他LARP家族成员一样,有多种潜在的LARP1 mRNA异构体似乎在细胞核内被剪接。细胞调节这些明显“冗余”mRNA剪接和表达的能力暗示了LARP1表达的上下文特异性机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ada4/7928056/2902547edc41/KRNB_A_1744320_F0001_C.jpg

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