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A Sequence determinant in 3'UTR of mRNAs for Nuclear Retention by Paraspeckles
bioRxiv - Molecular Biology Pub Date : 2020-10-12 , DOI: 10.1101/2020.07.19.206417
Audrey Jacq , Denis Becquet , Bénédicte Boyer , Séverine Guillen , Maria-Montserrat Bello-Goutierrez , Marie-Pierre Blanchard , Claude Villard , Maya Belghazi , Manon Torres , Jean-Louis Franc , Anne-Marie François-Bellan

Paraspeckles are nuclear membraneless structures composed of a long non-coding RNA, Nuclear-Enriched-Abundant-Transcript-1 and RNA binding proteins, which associate numerous mRNAs. It is therefore believed that their cellular function is to sequester in the nucleus their associated proteins and/or target mRNAs. However, little is known about the molecular determinant in mRNA targets that allow their association to paraspeckles except that inverted repeats of Alu sequences (IRAlu) present in 3'UTR of mRNAs may allow this association. While in a previous study we established the list of paraspeckle target RNAs in a rat pituitary cell line, we didn't find however, inverted repeated SINEs, the rat equivalent of primate IRAlus in 3'UTR of these RNAs. By developing a candidate gene strategy, we selected a paraspeckle target gene, namely calreticulin mRNA, and we searched for other potential RNA recruitment elements in its 3'UTR, since 3'UTRs usually contain the sequence recognition for nuclear localization. We found a 15-nucleotide sequence, present as a tandem repeat in 3'UTR of this mRNA, which is involved in the nuclear retention by paraspeckles. While being not overrepresented in the 3'UTR of the paraspeckle target RNAs, this recruitment element was present in near 30% of all 3'UTR mRNAs. In addition, since a oligonucleotide containing this sequence binds the paraspeckle protein component HNRNPK, it is proposed that HNRNPK may constitute a bridging protein between paraspeckles and target mRNAs.

中文翻译:

3'UTR mRNA的序列决定子旁斑的核保留。

副斑点是无核的无核膜结构,由长的非编码RNA,核富集丰富的转录物1和RNA结合蛋白组成,它们结合了许多mRNA。因此,据信它们的细胞功能是将其相关蛋白和/或靶mRNA隔离在细胞核中。然而,关于mRNA靶标中允许其与副斑点相关的分子决定子知之甚少,除了存在于mRNA的3'UTR中的Alu序列的反向重复序列(IRAlu)可以允许这种相关。虽然在先前的研究中我们建立了大鼠垂体细胞系中散斑靶RNA的列表,但是我们没有发现反向重复的SINE,即这些RNA 3'UTR中与灵长类动物IRAlus相当的大鼠。通过制定候选基因策略,我们选择了散斑目标基因,即钙网蛋白mRNA,我们在其3'UTR中寻找其他潜在的RNA募集元件,因为3'UTR通常包含核定位的序列识别。我们发现了一个15个核苷酸的序列,作为该mRNA的3'UTR中的串联重复序列存在,该序列参与了副斑点的核保留。虽然在散斑靶RNA的3'UTR中没有过度表达,但是该募集元件存在于所有3'UTR mRNA的近30%中。另外,由于包含该序列的寡核苷酸结合了副斑点蛋白组分HNRNPK,因此提出了HNRNPK可以构成副斑点和靶mRNA之间的桥接蛋白。UTR通常包含用于核定位的序列识别。我们发现了一个15个核苷酸的序列,作为该mRNA的3'UTR中的串联重复序列存在,该序列参与了副斑点的核保留。虽然在散斑靶标RNA的3'UTR中没有过度表达,但是该募集元件存在于所有3'UTR mRNA的近30%中。另外,由于包含该序列的寡核苷酸结合了副斑点蛋白组分HNRNPK,因此提出了HNRNPK可以构成副斑点和靶mRNA之间的桥接蛋白。UTR通常包含用于核定位的序列识别。我们发现了一个15个核苷酸的序列,以串联重复的形式存在于该mRNA的3'UTR中,该序列参与了副斑点的核保留。尽管在散斑靶RNA的3'UTR中并未过度表达,但该募集元件存在于所有3'UTR mRNA的近30%中。另外,由于包含该序列的寡核苷酸结合了副斑点蛋白组分HNRNPK,因此提出了HNRNPK可以构成副斑点和靶mRNA之间的桥接蛋白。该募集元素存在于所有3'UTR mRNA的近30%中。另外,由于包含该序列的寡核苷酸结合了副斑点蛋白组分HNRNPK,因此提出了HNRNPK可以构成副斑点和靶mRNA之间的桥接蛋白。该募集元素存在于所有3'UTR mRNA的近30%中。另外,由于包含该序列的寡核苷酸结合了副斑点蛋白组分HNRNPK,因此提出了HNRNPK可以构成副斑点和靶mRNA之间的桥接蛋白。
更新日期:2020-10-12
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