Kremp Marco, Bittner Elena, Martorana Domenica, Klingenberger Alexander, Stehlik Thorsten, Bölker Michael, Freitag Johannes
Department of Biology, Philipps-University Marburg, Marburg, Germany.
LOEWE Center for Synthetic Microbiology, Marburg, Germany.
Front Cell Dev Biol. 2020 May 5;8:251. doi: 10.3389/fcell.2020.00251. eCollection 2020.
Proteins destined for transport to specific organelles usually contain targeting information, which are embedded in their sequence. Many enzymes are required in more than one cellular compartment and different molecular mechanisms are used to achieve dual localization. Here we report a cryptic type 2 peroxisomal targeting signal encoded in the 5' untranslated region of fungal genes coding for 6-phosphogluconate dehydrogenase (PGD), a key enzyme of the oxidative pentose phosphate pathway. The conservation of the cryptic PTS2 motif suggests a biological function. We observed that translation from a non-AUG start codon generates an N-terminally extended peroxisomal isoform of PGD. Non-canonical initiation occurred at the sequence AGG AUU, consisting of two near-cognate start codons in tandem. Taken together, our data reveal non-AUG translation initiation as an additional mechanism to achieve the dual localization of a protein required both in the cytosol and the peroxisomes.
destined for transport to specific organelles usually contain targeting information, which are embedded in their sequence. Many enzymes are required in more than one cellular compartment and different molecular mechanisms are used to achieve dual localization. Here we report a cryptic type 2 peroxisomal targeting signal encoded in the 5' untranslated region of fungal genes coding for 6-phosphogluconate dehydrogenase (PGD), a key enzyme of the oxidative pentose phosphate pathway. The conservation of the cryptic PTS2 motif suggests a biological function. We observed that translation from a non-AUG start codon generates an N-terminally extended peroxisomal isoform of PGD. Non-canonical initiation occurred at the sequence AGG AUU, consisting of two near-cognate start codons in tandem. Taken together, our data reveal non-AUG translation initiation as an additional mechanism to achieve the dual localization of a protein required both in the cytosol and the peroxisomes.
蛋白质若要运输到特定细胞器，通常会包含嵌入其序列中的靶向信息。许多酶在不止一个细胞区室中发挥作用，且会利用不同的分子机制来实现双重定位。在这里，我们报告了一种隐藏的2型过氧化物酶体靶向信号，它编码于真菌基因的5'非翻译区，该基因编码6-磷酸葡萄糖酸脱氢酶（PGD），这是氧化戊糖磷酸途径的一种关键酶。隐藏的PTS2基序的保守性表明其具有生物学功能。我们观察到，从非AUG起始密码子开始翻译会产生PGD的N端延伸过氧化物酶体异构体。非经典起始发生在AGG AUU序列处，该序列由两个串联的近同源起始密码子组成。综合来看，我们的数据揭示了非AUG翻译起始是实现一种在细胞质溶胶和过氧化物酶体中都需要的蛋白质双重定位的额外机制。
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