¹ÚÅ׸®¾Æ ncRNA¸¦ ÅëÇÑ ½ºÆ®·¹½ºÀÇ Á¶Àý
Çѱ¹°úÇбâ¼ú¿ø ÀÌ¿µÈÆ ±³¼ö
1. °³¿ä
¹ÚÅ׸®¾Æ´Â »ýÁ¸À» À§ÇùÇÏ´Â ¿©·¯ °¡Áö ȯ°æ½ºÆ®·¹½º¿¡ ³ëÃ⠵ǰí ÀÖ°í, À̸¦ ±Øº¹Çϱâ À§ÇÑ ´Ù¾çÇÑ ¹æ¹ýÀ» »ç¿ëÇÏ°í ÀÖ´Ù. ȯ°æº¯È¸¦ °¨ÁöÇÏ¿© ´Ù¾çÇÑ À¯ÀüÀÚÀÇ ¹ßÇö°ú ´Ü¹éÁúµéÀÇ È°¼ºÀ» Á¶ÀýÇÏ´Â ½ÅÈ£Àü´Þ ü°è¸¦ Á¶Á¤ÇÑ´Ù. ¼¼Æ÷³»ÀÇ RNA À¯Àüü (RNomics) ºÐ¼®À» ÅëÇؼ, ´Ü¹éÁú ÇÕ¼ºÁ¤º¸¸¦ ¾ÏÈ£ÈÇÏ°í ÀÖ´Â messenger RNAs (mRNAs)¿Ü¿¡ ¼¼Æ÷ ´ë»çÁ¶Àý¿¡ °ü¿©ÇÏ´Â ´Ù¾çÇÑ Å¸ÀÔÀÇ RNA°¡ Á¸ÀçÇÏ°í ÀÖÀ½ÀÌ ¾Ë·ÁÁ³´Ù. ´Ù¾çÇÑ ¹ÚÅ׸®¾Æ¿¡¼ Áö¼ÓÀûÀ¸·Î ¹àÇôÁö°í ÀÖ´Â ÀÌ·¯ÇÑ ÀÛÀº ´Ü¹éÁúÀ» ÄÚµåÇÏÁö ¾Ê´Â ÀÛÀº RNA (small non-coding RNA: ncRNA)µéÀº ±âÁ¸ÀÇ 2°³-ÀÎÀÚ ½ÅÈ£Àü´Þ°è (two-component signal transduction system) ¹× ´Ù¾çÇÑ Á¶Àý´Ü¹éÁú°ú ´õºÒ¾î ½ºÆ®·¹½º ´ëÀÀÀ» À§ÇÑ Çٽɿä¼Ò·Î½áÀÇ ±â´ÉÀ» ÇÏ°í ÀÖ´Â °æ¿ì°¡ ¸¹¾Ò´Ù. (Abu-Qatouseh et al., 2010; Altuvia, 2007; Pichon and Felden, 2008; Raabe et al., 2011). °¡Àå Àß Á¤¸³µÇ¾î ÀÖ´Â ncRNAÀÇ ÀÛ¿ë±âÀÛÀº Ÿ°Ù mRNA¿Í ¿°±â½ÖÀ» ÀÌ·ç°Å³ª Ÿ°Ù ´Ü¹éÁú°ú »óÈ£ÀÛ¿ëÇÏ¿© RNA-´Ü¹éÁú º¹ÇÕü (Ribonucleoprotein; RNP)¸¦ ¸¸µå´Â °ÍÀÌ´Ù. ncRNA´Â À¯Àüü »ó¿¡ Á¸ÀçÇÏ´Â À§Ä¡¿¡ µû¶ó¼ ½Ã½º·Î ÄÚµåµÇ´Â (cis-encoded) ncRNA ¶Ç´Â Æ®·£½º·Î ÄÚµåµÇ´Â (trans-encoded ncRNA)·Î ºÐ·ùÇϱ⵵ ÇÑ´Ù. ½Ã½º·Î ÄÚµåµÇ´Â ncRNA´Â Ÿ°Ù mRNAÀÇ ¹Ù·Î ¹Ý´ë°¡´Ú¿¡ Á¸ÀçÇÏ´Â ncRNA·Î Ÿ°Ù mRNA¿Í ¿ÏÀüÇÑ ¿°±â½ÖÀ» ÀÌ·ê ¼ö ÀÖ´Â ¹Ý¸é, Ÿ°Ù mRNA À¯ÀüÀÚ¿Í ¸Ö¸® ¶³¾îÁø À¯ÀüÀÚ¿¡¼ Æ®·£½º·Î ÄÚµåµÇ´Â ncRNA´Â Ÿ°Ù mRNA¿Í ºÎºÐÀûÀÎ ¿°±â½ÖÀ» ÀÌ·é´Ù (Richards and Vanderpool, 2011). Æ®·£½º ÄÚµåµÇ´Â ncRNAÀÇ °æ¿ì, ±â´ÉÀ» À§Çؼ »þÆä·Ð ´Ü¹éÁúÀÎ Hfq°¡ ÇÊ¿äÇÑ °æ¿ì°¡ ¸¹´Ù. 102°³ ¾Æ¹Ì³ë»êÀ¸·Î ÀÌ·ç¾îÁø Hfq ´Ü¹éÁúÀº AU°¡ ¸¹Àº ´ÜÀÏ°¡´Ú¼º RNA¿Í »óÈ£ÀÛ¿ëÇÑ´Ù°í ¾Ë·ÁÁ® Àִµ¥ (Geissmann et al., 2006; Moller et al., 2002), ¹ÚÅ׸®¾Æ Á¾°£¿¡ º¸Á¸¼ºÀÌ ³ôÀ¸¸ç ½ºÆ®·¹½º ´ëÀÀÀ» Æ÷ÇÔÇÑ ´Ù¾çÇÑ ¼¼Æ÷±â´É¿¡ ¿µÇâÀ» ¹ÌÄ£´Ù. hfq µ¹¿¬º¯ÀÌ´Â ´Ù¾çÇÑ º´¿ø¼º ¹ÚÅ׸®¾ÆÀÇ º´¿ø¼ºÀ» ¸Å¿ì °¨¼Ò½ÃŲ´Ù. mRNAÀÇ 5¡Ç ¸»´Ü ºñ¹ø¿ª ¿µ¿ª (5¡Ç untranslated regions; 5¡Ç UTR)Àº ±¸Á¶º¯È µîÀ» ÅëÇؼ mRNAÀÇ ¹ßÇöÀ» Á¶ÀýÇÏ´Â °æ¿ì°¡ ¸¹Àºµ¥, ncRNA°¡ ÀνÄÇϴ Ÿ°Ù¿µ¿ª ¶ÇÇÑ 5¡Ç UTRÀÌ µÇ´Â °æ¿ì°¡ ¸¹¾Ò´Ù. º» ¿¬±¸µ¿Çâ¿¡¼´Â ¹ÚÅ׸®¾Æ ncRNA°¡ ½ºÆ®·¹½º¿¡ ´ëÀÀÇϱâ À§ÇÏ À§ÇÏ¿© ¼¼Æ÷´ë»ç¿¡ ¾î¶»°Ô °ü¿©ÇÏ°í ÀÖ´ÂÁö¸¦ ¸î°¡Áö ½ÇÇè °á±«µéÀÇ ¿¹¸¦ ÅëÇØ »ìÆ캸°íÀÚ ÇÑ´Ù.
2. ¿Âµµ ½ºÆ®·¹½º¿Í ncRNA
¹ÚÅ׸®¾Æ´Â ¿Âµµº¯È¿¡ ¹Î°¨ÇÏ°Ô ´ëÀÀÇϱâ À§ÇÑ º¹ÀâÇÑ Çǵå¹é Á¶Àý±âÀÛµéÀ» °¡Áö°í ÀÖ´Ù. ¡®RNA ¿Âµµ°è (RNA thermometers)¡¯¶ó°í ºÎ¸£´Â RNA ¿µ¿ªÀÇ ¿Âµµ¿¡ µû¸¥ ±¸Á¶º¯È¸¦ ÅëÇÑ Çǵå¹é ½Ã½ºÅÛÀº, ¿Âµµº¯È¿¡ ºü¸£°Ô ´ëÀÀÇÒ ¼ö ÀÖ´Ù. RNA ¿Âµµ°è´Â ÁÖ·Î 5¡Ç UTR ¿µ¿ª¿¡¼ ¸®º¸Á» °áÇÕÀÚ¸®¸¦ Æó¼âÇÏ´Â ÇüÅ·Π2Â÷±¸Á¶¸¦ Çü¼ºÇÏ°í ÀÖ´Ù°¡, ³ôÀº ¿Âµµ¿¡¼ ±¸Á¶°¡ º¯ÈÇÏ¿© ´Ü¹éÁú ¹ßÇöÀÌ °¡´ÉÇϵµ·Ï ÇÑ´Ù (Kortmann and Narberhaus, 2012). ROSE ¿ä¼Ò (Repression of the heat shock gene expression element: ROSE)´Â ¿Ãæ°Ý ´Ü¹éÁú¿¡¼ ÈçÇÏ°Ô ³ªÅ¸³ª´Â RNA ¿Âµµ°èÁß Çϳª·Î, SD ¼¿ (Shine-Dalgarno sequence) ±Ùó¿¡ U(U/C)GCU °øÅ뼿À» °®°í 60~100 ntÀÇ ¿µ¿ªÀ¸·Î Á¸ÀçÇÑ´Ù. 2°³ ÀÌ»óÀÇ ¸Ó¸®ÇÉ ±¸Á¶°¡ Æ÷ÇԵǴµ¥, SD ¼¿À» Æ÷ÇÔÇÏ´Â 3¡Ç ¸Ó¸®Çɱ¸Á¶°¡ °í¿Â¿¡¼ Ç®¾îÁö¸é¼ mRNA ¹ø¿ªÀ» ÃËÁø½ÃŲ´Ù (Waldminghaus et al., 2009). 4U ¿ä¼Ò (fourU element)´Â Salmonella agsA (aggregation suppressing A) mRNAÀÇ 5¡Ç UTR¿¡ ³ªÅ¸³ª´Âµ¥, ³·Àº ¿Âµµ¿¡¼ ³× °³ÀÇ ¿ì¸®µò ¿°±â¼¿ÀÌ SD ¼¿ÀÇ AGGA ¿°±â¼¿°ú ÇÔ²² ¸Ó¸®ÇÉ ±¸Á¶¸¦ Çü¼ºÇÑ´Ù. ¸¶Âù°¡Áö·Î ¿Âµµ°¡ ³ô¾ÆÁö¸é ±¸Á¶°¡ ºÒ¾ÈÁ¤ÇØÁö°í mRNAÀÇ ¹ßÇöÀÌ ÃËÁøµÈ´Ù.
RNA ¿Âµµ°è´Â Àú¿Â ½ºÆ®·¹½º¿¡¼µµ Áß¿äÇÑ ±â´ÉÀ» ÇÑ´Ù. Àú¿Â¿¡¼ ¹ßÇöµÇ¾î RNA »þÆä·ÐÀÇ ±â´ÉÀ» ÇÏ´Â CspAÀÇ °æ¿ì, Àú¿Â¿¡¼ ¿ÏÀüÈ÷ ´Ù¸¥ ÇüÅÂÀÇ 5¡Ç UTR ±¸Á¶¸¦ °¡ÁüÀ¸·Î½á ¼¼Æ÷³» mRNAÀÇ ¾ÈÁ¤¼ºÀÌ Áõ°¡µÇ¾î ´Ü¹éÁú ¹ßÇöÀÌ Áõ°¡µÈ´Ù (Giuliodori et al., 2010).
Æ®·£½º·Î ÄÚµåµÇ´Â ncRNAÀÎ DsrA´Â µÎ°¡Áö Àü»çüÀÇ ÇüÅ·ΠÁ¸ÀçÇϴµ¥, ¿Âµµº¯È¿¡ µû¶ó µÎ°¡Áö Àü»çüÀÇ ºñÀ²ÀÌ ´Þ¶óÁö°í, À̸¦ ÅëÇØ ½ºÆ®·¹½º ´ëÀÀÀ» À§ÇÑ RpoSÀÇ ¹ßÇöÀ» ÃËÁø½ÃŲ´Ù (Repoila and Gottesman, 2001).
Åä¾ç¹Ì»ý¹°ÀÎ L. monocytogenesÀÇ prfA mRNAÀÇ °æ¿ì, »ç¶÷ÀÇ Ã¼¿ÂÀÎ 37¡É¿¡¼ 5¡ÇUTRÀÇ ±¸Á¶°¡ º¯ÈµÇ¸é ¹ßÇöÀÌ ÃËÁøµÇ°í º´¿ø¼ºÀ» ÀÏÀ¸Å°´Â ¿©·¯ °¡Áö À¯ÀüÀÚ¸¦ ¹ßÇö½ÃÅ°°Ô µÈ´Ù (Johansson et al., 2002).
±×¸² 1. ¿Âµµ ½ºÆ®·¹½º¸¦ ±Øº¹Çϱâ À§ÇÑ ncRNAÀÇ ÀÛ¿ë±âÀÛ. agsA mRNA´Â RNA ¿Âµµ°èÀÎ 4U ¿ä¼Ò¸¦ ÅëÇؼ ³·Àº ¿Âµµ¿¡¼´Â ¸®º¸Á»ÀÇ °áÇÕÀÌ ÀúÇصǰí, ³ôÀº ¿Âµµ¿¡¼´Â ÁöÆÛ¿Í À¯»çÇÑ ¸ÞÄ¿´ÏÁòÀ¸·Î ºÒ¾ÈÁ¤ÈµÇ¾î ¸®º¸Á»ÀÇ °áÇÕÀÌ °¡´ÉÇØÁö°í À¯ÀüÀÚ°¡ ¹ßÇöµÈ´Ù.
3. ´ë»ç»ê¹°/¾çºÐ ½ºÆ®·¹½º¿Í ncRNA
¹Ì»ý¹°µéÀº Á¾Á¾ ¿µ¾ç°áÇÌÀ¸·Î ÀÎÇÑ ¼ºÀåÁ¤Ã¼»óÅ·Π¹ß°ßµÈ´Ù. ¼¼Æ÷³»¿¡ ±Û·çÄÚ¿À½º-6-Àλê (glucose-6-phosphate)ÀÌ ÃàÀûµÇ¸é ¼¼Æ÷¼ºÀåÀÌ ¸ØÃß°í Á×À½¿¡ À̸£±âµµ ÇÑ´Ù (Englesberg et al., 1962). ÀÌ·¯ÇÑ ½ºÆ®·¹½º »óÅ¿¡¼ Hfq-°áÇÕ ncRNA Áß ÇϳªÀÎ SgrS ncRNA°¡ ¹ßÇöµÇ°í, ±Û·çÄÚ¿À½º ¿î¹Ýü ÁßÀÇ Çϳª¸¦ ÄÚµåÇÏ´Â ptsG mRNA¿Í »óÈ£ÀÛ¿ëÇÏ¿© ¸®º¸Çٻ갡¼öºÐÇØÈ¿¼Ò E (RNase E) ÀÇÁ¸ÀûÀÎ ¹æ½ÄÀ¸·Î ptsG mRNA¸¦ ºÐÇØÇÑ´Ù (Maki et al., 2010; Morita et al., 2005). SgrS ncRNA´Â SgrT¶ó´Â ªÀº ÆéŸÀ̵带 ¹ßÇöÇϱ⵵ Çϴµ¥, SgrT´Â PtsG ´Ü¹éÁúÀÇ ±â´ÉÀ» ÀúÇØÇÑ´Ù (Wadler and Vanderpool, 2011).
ź¼ÒÀúÀå Á¶Àý½Ã½ºÅÛÀÇ ÇÙ½É ¿ªÇÒÀ» ÇÏ´Â CsrA ´Ü¹éÁúÀÇ È°¼ºÀº BarA/UvrY 2°³-ÀÎÀÚ ½ÅÈ£Àü´Þ°è¿¡ ÀÇÇؼ °£Á¢ÀûÀ¸·Î Á¶ÀýµÈ´Ù. ź¼Ò°áÇÌ»óȲ¿¡¼ UvrY¿¡ ÀÇÇØ µÎ°¡Áö ncRNA, CsrB¿Í CsrC°¡ ºü¸£°Ô ¹ßÇöµÇ´Âµ¥, ÀÌ µÎ°¡Áö ncRNA´Â ´Ù¼öÀÇ CsrA ´Ü¹éÁú °áÇÕÀÚ¸®¸¦ °®°í ÀÖ¾î¼ CsrA ´Ü¹éÁú°ú °áÇÕÇÔÀ¸·Î½á ÇØ´çÀÛ¿ë¿¡ °ü¿©ÇÏ´Â À¯ÀüÀÚÀÇ ¹ßÇöÀ» ÀúÇØÇÏ°í, ±Û·çÄÚ¿À½º ½Å»ýÇÕ¼º¿¡ °ü¿©ÇÏ´Â À¯ÀüÀÚµéÀ» ¹ßÇöÇÑ´Ù (Pernestig et al., 2003).
Caulobacter crescentusÀÇ CrfA ncRNA´Â ź¼Ò°áÇÌ »óȲ¿¡¼ ¹ßÇöµÇ¾î CC3461 ¼ö¿ë±â mRNAÀÇ 5¡Ç UTR°ú ¿°±â½ÖÀ» ÀÌ·ç¾î, mRNAÀÇ ¼¼Æ÷³» ¾ÈÁ¤¼ºÀ» Áõ°¡½ÃÄѼ ´õ ´Ù¾çÇÑ Á¾·ùÀÇ Åº¼Ò¿øÀÌ ¼¼Æ÷³»·Î À¯À﵃ ¼ö ÀÖµµ·Ï ÇÑ´Ù (Landt et al., 2010).
Staphylococcus, Macrococcus, Bacillusµî¿¡¼ Àß º¸Á¸µÇ¾î ÀÖ´Â RsaE ncRNA´Â ¾çºÐÀÌ ºÎÁ·ÇØÁö´Â Áö¼ö¼ºÀå±â ÈĹݺο¡¼ ¹ßÇöÀÌ Áõ°¡µÈ´Ù. 17 ntÀÇ ´ÜÀÏ°¡´ÚºÎºÐ ¾çÂÊÀ¸·Î ¸Ó¸®Çɱ¸Á¶¸¦ Çü¼ºÇÏ°í ÀÖ´Â ÀÌ ncRNA´Â, opp3 ¿ÀÆä·ÐÀÇ Ã³À½°ú ¸¶Áö¸· mRNAÀÎ opp3B, opp3A¿Í ¿°±â½ÖÀ» ÀÌ·ç¾î ¹ßÇöÀ» ÀúÇؽÃÄѼ ¿µ¾ç°áÇÌ»óÅ¿¡ Àß ÀûÀÀÇÒ ¼ö ÀÖµµ·Ï ÇÑ´Ù (Bohn et al., 2010).
¾Æ¹Ì³ë»êÀÇ ´ë»ç´Â ÇÙ»êÀ̳ª È¿¼Ò º¸Á¶ÀÎÀÚµîÀÇ »ý¼º¿¡ ÇʼöÀûÀ̱⠶§¹®¿¡ Á¤È®ÇÏ°Ô Á¦¾îµÉ ÇÊ¿ä°¡ ÀÖ´Ù. Gcv ¿ÀÆä·Ð (glycine cleavage operon)ÀÎ gcvTHP ¿ÀÆä·ÐÀº ±Û¶óÀ̽ÅÀ» ´ë»ç½ÃÄÑ ¼¼Æ÷³» ź¼Ò¿ø»ýÇÕ¼º¿¡ ÀÌ¿ëµÇ´Â 5,10-¸ÞÆ¿·»Å×Æ®¶óÇÏÀ̵å·Î¿±»êÀ» »ý¼ºÇϴµ¥ ÇʼöÀûÀÌ´Ù. ¼¼Æ÷³»¿¡ ±Û¶óÀ̽Š³óµµ°¡ ³ô¾ÆÁö¸é Hfq¿Í »óÈ£ÀÛ¿ëÇÏ´Â GcvB ncRNAÀÇ ¹ßÇöÀÌ È°¼ºÈµÇ°í ªÀº ÆéŸÀ̵峪, ´Ù¸¥ ¾Æ¹Ì³ë»ê, µ¶¼º¹°Áú°ú Ç×»ýÁ¦µîÀÇ ¼¼Æ÷À¯ÀÔ¿¡ °ü¿©µÇ´Â À¯ÀüÀÚµéÀÇ ¹ßÇöÀ» ¾ïÁ¦ÇÑ´Ù (Urbanowski et al., 2000). GcvB ncRNA´Â mRNA Ÿ°ÙµéÀ» Á¶ÀýÇÏ´Â µÎ°¡Áö ¾ÈƼ¼¾½º¿µ¿ªÀ» °¡Áö°í Àִµ¥, ~1%ÀÇ Salmonella mRNA°¡ G/U°¡ ¸¹Àº ¿µ¿ªÀ» ÅëÇØ Á¶ÀýµÊÀÌ º¸°íµÇ¾ú°í, cycA mRNA´Â µÎ°¡Áö ¾ÈƼ¼¾½º¿µ¿ªÀ» ¸ðµÎ »ç¿ëÇÏ¿© Á¶ÀýµÈ´Ù. À̴ Ÿ°Ù mRNA¿Í ¿°±â½ÖÀ» ÀÌ·ç´Â À¯¿¬¼ºÀ» ³ªÅ¸³»ÁÖ´Â ¿¹·Î ¾ÕÀ¸·Î ´õ ´Ù¾çÇÑ Å¸°Ù mRNA°¡ ã¾ÆÁú ¼ö ÀÖÀ½À» ÀǹÌÇÑ´Ù.
±×¸² 2. ÀϹÝÀûÀÎ ¼ºÀåÁ¶°Ç¿¡¼ CsrA ´Ü¹éÁúÀº ÇØ´çÀÛ¿ë¿¡ ÇÊ¿äÇÑ À¯ÀüÀÚ¸¦ ¹ßÇö½ÃÅ°°í, ±Û·çÄÚ¿À½º ½Å»ýÇÕ¼º¿¡ °ü·ÃµÈ À¯ÀüÀÚµéÀÇ ¹ßÇöÀ» ÀúÇØÇÑ´Ù. ź¼Ò¿øÀÌ ºÎÁ·ÇÑ ½ºÆ®·¹½º »óȲ¿¡¼ CsrB/CsrC ncRNA´Â CsrA¿¡ °áÇÕÇÏ¿© CsrAÀÇ È°µ¿À» ¹æÇØÇÑ´Ù. ½ºÆ®·¹½º»óȲ¿¡¼ ¹þ¾î³ª¸é CsrB/CsrC´Â CsrD¿Í RNase E¸¦ ¸Å°³·ÎÇÏ¿© ºÐÇصȴÙ.
4. ¼¼Æ÷¸· ½ºÆ®·¹½º¿Í ncRNA
±×¶÷À½¼º ¹ÚÅ׸®¾ÆÀÇ ¼¼Æ÷¿Ü¸· (outer membrane; OM)Àº µ¶¼º¹°ÁúÀÇ À¯ÀÔÀ» ¸·´Â Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù. Æ÷¸° ´Ü¹éÁúµéÀº OM¿¡ Åë·Î¸¦ ¸¸µé¾î ¾çºÐÀ» Èí¼öÇÏ°í Æó±â¹°À» ¹èÃâÇÑ´Ù. E. coli¿Í Salmonella¿¡¼´Â ¥òE ÀÎÀÚ ½ÅÈ£Àü´Þü°è¸¦ ÅëÇؼ OM ´Ü¹éÁúµéÀÇ »óÅ°¡ °¨½ÃµÈ´Ù. À߸ø Çü¼ºµÈ OM ´Ü¹éÁúµé (¼¼Æ÷¸· ½ºÆ®·¹½º¸¦ ¾ß±â)ÀÌ ¸¹¾ÆÁö¸é ¥òE ÀÎÀÚ°¡ È°¼ºÈµÈ´Ù. Àå³»¹ÚÅ׸®¾Æ¿¡¼ º¸Á¸¼ºÀÌ ¸Å¿ì ³ôÀº OmpA ´Ü¹éÁúÀº ¼ºÀåÁ¤Áö±â¿¡¼ Æ®·£½º·Î ÄÚµåµÇ´Â ncRNAÀÎ MicA¿¡ ÀÇÇؼ RNase E ÀÇÁ¸ÀûÀ¸·Î ±Þ°ÝÈ÷ ¹ßÇöÀÌ ÀúÇصȴ٠(Rasmussen et al., 2005). ¥òE ÀÎÀÚ¿¡ ÀÇÇØ ¹ßÇöµÇ´Â ¶Ç ´Ù¸¥ ncRNAÀÎ RybB ncRNA ¶ÇÇÑ ´Ù¼öÀÇ OM ´Ü¹éÁúµéÀÇ ¹ßÇöÀ» Á¶ÀýÇÏ¿© ¼¼Æ÷¸· ½ºÆ®·¹½º »óȲ¿¡¼ OM ´Ü¹éÁúµéÀÇ ¾çÀ» º¯È½ÃŲ´Ù (Papenfort et al., 2010). CyaR ncRNA´Â ompX mRNAÀÇ ¹ø¿ªÀ» ¾ïÁ¦Çϸç, V. choleraeÀÇ VrrA ncRNAµµ OmpAÀÇ ¹ßÇöÀ» ÀúÇؽÃÅ°°í, OMV (outer membrane vesicle)ÀÇ »ý¼ºµµ ÃËÁø½ÃÄÑ ¼¼Æ÷¸· ½ºÆ®·¹½º¸¦ ´õ¿í ¿ÏÈÇÑ´Ù.
±×¸² 3. Æ®·£½º·Î ÄÚµåµÇ´Â ncRNAÀÎ VrrA´Â ¼¼Æ÷¸· ½ºÆ®·¹½º¿¡ ´ëÀÀÇÏ¿© ¹ßÇöÀÌ À¯µµµÈ´Ù. VrrA ncRNA´Â ompT, tcpA, ompA mRNAÀÇ ¸®º¸Á» °áÇÕÀÚ¸®¿µ¿ª¿¡ °áÇÕÇÏ¿© À¯ÀüÀÚ ¹ßÇöÀ» ÀúÇØÇÑ´Ù.
5. »êȽºÆ®·¹½º¿Í ncRNA
OxyR Àü»çÀÎÀÚ´Â H2O2¿¡ ÀÇÇؼ Ƽ¿Ã-ÀÌÈ²È »êÈȯ¿ø (thiol-disulfide redox) ½ºÀ§Ä¡¸¦ ÅëÇØ È°¼ºÈµÇ¾î, Ä«Å»¶ó¾ÆÁ¦ (catalase), ¼ö»êÈ°ú»êȹ° ȯ¿øÈ¿¼Ò, ÃÊ»êȹ° ºÒ±ÕµîÈÈ¿¼Ò (superoxide dismutase) µîÀÇ ¹ßÇöÀ» Áõ°¡½ÃÄѼ »êȽºÆ®·¹½º¿¡¼ ¼¼Æ÷¸¦ º¸È£ÇÑ´Ù (Pomposiello and Demple, 2001). OxyS ncRNA´Â »êȽºÆ®·¹½º·Î ÀÎÇؼ ¹ßÇöÀÌ À¯µµµÇ¾î ¸¹Àº À¯ÀüÀÚµéÀÇ ¹ßÇöÀ» Á¶ÀýÇÏ°í µ¹¿¬º¯ÀÌ°¡ À¯¹ßµÇ´Â °ÍÀ» ¾ïÁ¦ÇÑ´Ù (Altuvia et al., 1997).
¸¹Àº º´¿ø¼º ¹ÚÅ׸®¾ÆµéÀº ¼÷ÁÖÀÇ ´ë½Ä¼¼Æ÷¾È¿¡¼ »êȽºÆ®·¹½º¿¡ ³ëÃâµÇ°Ô µÇ´Âµ¥, B11, B55, F6, ASpks¿Í °°Àº ncRNAµéÀÌ °¨¿° Ãʱ⿡ ¹ßÇöµÇ¾î¼ ´Ù¾çÇÑ À¯ÀüÀÚÀÇ ¹ßÇöÀ» Á¶ÀýÇÑ´Ù (Arnvig and Young, 2009).
6. öºÐºÎÁ· ½ºÆ®·¹½º¿Í ncRNA
öºÐÀº ¼¼Æ÷¼ºÁ¤°ú ºÐÈ, ÀüÀÚÀü´Þ°è, »ê¼Ò¿î¹Ý, ¼¼Æ÷´ë»ç, Çص¶µîÀÇ ¼¼Æ÷È°µ¿¿¡ ¹Ýµå½Ã ÇÊ¿äÇÑ ¿ä¼ÒÀÌ´Ù. ÇÏÁö¸¸ ³ôÀº ³óµµÀÇ Ã¶ºÐÀº È°¼º»ê¼ÒÀÇ Çü¼ºÀ» À¯¹ßÇÏ¿© ¼¼Æ÷¿¡ Çظ¦ ³¢Ä¡±âµµ ÇÑ´Ù. ´ëºÎºÐÀÇ ¹ÚÅ׸®¾Æ¿¡¼ Fur (ferric uptake regulator) ´Ü¹éÁúÀº öºÐÀÇ Ç×»ó¼º À¯Áö¿¡ Á߽ɱâ´ÉÀ» ¸Ã°í ÀÖ´Ù. öºÐÀÌ ÃæºÐÇÒ ¶§´Â öºÐ Èí¼ö À¯ÀüÀÚµéÀ» ¾ïÁ¦ÇÏ°í, öºÐ ÀúÀå ´Ü¹éÁúµéÀÇ ¹ßÇöÀ» Áõ°¡½ÃŲ´Ù. RyhB ncRNA´Â öºÐºÎÁ· ½ºÆ®·¹½º¿¡¼ ¹ßÇöµÇ´Â ncRNA·Î Fur ´Ü¹éÁú¿¡ ÀÇÇØ ¹ßÇöÀÌ Á¶ÀýµÈ´Ù. öºÐÀÌ Ç³ºÎÇÒ ¶§ RyhB ncRNAÀÇ ¹ßÇöÀÌ À¯µµµÇ°í sdhCDAB, acnA, fumA, bfr, ftnA, sodB mRNA µî öºÐ´ë»ç¿Í °ü¿©µÈ 18°³ ¿ÀÆä·Ð, 56°³ ´Ü¹éÁúÀÇ ¹ßÇöÀ» Á¶ÀýÇÑ´Ù (Masse et al., 2005). RyhB ncRNA´Â fur mRNAÀÇ ¹ßÇöµµ ¾ïÁ¦ÇÏ´Â À½¼ºÇǵå¹é½Ã½ºÅÛµµ º¸¿©Áشٴ Á¡ÀÌ ÁÖ¸ñÇÒ ¸¸ÇÏ´Ù (Vecerek et al., 2007).
V. cholerae, S. flexneri, S. dysenteriae µî¿¡¼ RyhB ncRNAÀÇ »óµ¿Ã¼°¡ ¹ß°ßµÇ°í ÀÖ´Ù. ±× ±â´Éµµ ´õ ´Ù¾çÇÏ°Ô ¹àÇôÁ®¼ ¹ÙÀÌ¿ÀÇʸ§ Çü¼ºÀ̳ª ÁÖȼº ¿òÁ÷ÀÓ¿¡µµ °ü¿©ÇÏ°í ÀÖ°í (Davis et al., 2005; Mey et al., 2005), ³»»ê¼ºÀÇ °¨¼Ò¿Í º´¿ø¼º ¾ïÁ¦¿¡µµ °ü¿©ÇÑ´Ù (Murphy and Payne, 2007).
7. pH ½ºÆ®·¹½º¿Í ncRNA
À§»êÀÇ ±ØÇѻ꼺Á¶°ÇÀ» °ßµ®³»´Â °ÍÀº ¹ÚÅ׸®¾ÆµéÀÌ Àå³»¿¡ Á¤ÂøÇϱâ À§ÇØ Áß¿äÇÏ´Ù. ¸î¸î ±×¶÷¾ç¼º±Õ ¹× ±×¶÷À½¼º±ÕÀº ±Û·çŽ»êÀ» ÀÌ¿ëÇÑ ³»»ê¼º ½Ã½ºÅÛ (gad system)À» °¡Áö°í ÀÖ¾î¼ ³ôÀº ³óµµÀÇ H+ ½ºÆ®·¹½º·ÎºÎÅÍ ¼¼Æ÷¸¦ º¸È£ÇÒ ¼ö ÀÖ´Ù. GadA, GadB µÎ °³ÀÇ ±Û·çŽ»ê Żī¸£º¹½ÇÈÈ¿¼Ò´Â ±Û·çŽ»êÀ» ÀÌ¿ëÇØ ¥ã-¾Æ¹Ì³ëºÎÆ¿»êÀ» ¸¸µé¸é¼ H+¸¦ Á¦°ÅÇÑ´Ù. GadE, GadX, GadW, CRP, H-NS, ¥òS µîÀÌ º¹ÀâÇÏ°Ô °ü¿©ÇÏ¿© ³»»ê¼º½Ã½ºÅÛÀ» Á¶ÀýÇÑ´Ù. E. coli¿¡¼ Hfq¿Í »óÈ£ÀÛ¿ëÇÏ´Â GadY ncRNA´Â gadX mRNAÀÇ 3¡Ç ¸»´ÜºÎÀ§¿¡ ½Ã½º·Î ÄÚµåµÇ´Â ncRNA·Î gadX mRNAÀÇ 3¡Ç ºÎÀ§¿¡ »óº¸ÀûÀ¸·Î °áÇÕÇÏ¿© mRNA¸¦ RNase EÀÇ ºÐÇطκÎÅÍ º¸È£ÇÑ´Ù (Opdyke et al., 2004). GadXÀÇ ÃàÀûÀº ÇÏÀ§ÀÇ ³»»ê¼º °ü·ÃÀ¯ÀüÀÚ¸¦ ¹ßÇö½ÃÄÑ ³·Àº pH¿¡¼ »ýÁ¸¼ºÀ» Áõ°¡½ÃŲ´Ù (Opdyke et al., 2011). GcvB ncRNA ¶ÇÇÑ ¾Ë ¼ö ¾ø´Â ±âÀÛÀ¸·Î ¥òS ÀÇ ¹ßÇöÀ» Áõ°¡½ÃÄÑ ³·Àº pH¿¡¼ÀÇ »ýÁ¸¼ºÀ» Áõ°¡½ÃÅ°¸ç (Jin et al., 2009), ArcZ, DsrA, RprA ncRNA¸¦ ÅëÇÑ ¥òS ÀÇ ¹ßÇöÁõ°¡ ¿ª½Ã pH 2.0¿¡¼ÀÇ ¼¼Æ÷ÀÇ »ýÁ¸¼º¿¡ Å« ¿µÇâÀ» ¹ÌÄ£´Ù (Bak et al., 2014). ³ôÀº pH¿¡¼´Â ¾Æ¹Ì³ë»ê Å»¾Æ¹ÎÈ¿Í ´ç¹ßÈ¿¸¦ ÅëÇÑ »ê »ý¼ºÁõ°¡, ¼¼Æ÷¸·ÀÇ Æ¯¼ºº¯È µîÀ» ÅëÇØ ½ºÆ®·¹½º¸¦ ±Øº¹ÇÑ´Ù. alx mRNAÀÇ 5¡Ç UTR¿¡´Â PRE ¸®º¸ ½ºÀ§Ä¡ (pH responsive RNA element)°¡ ÀÖ¾î¼ ³ôÀº pH¿¡¼¸¸ Alx ´Ü¹éÁúÀ» ¹ßÇö½ÃŲ´Ù (Nechooshtan et al., 2009).
8. CRISPR: ½ºÆ®·¹½º °ü¸®¸¦ À§ÇÑ »õ·Î¿î ±âÀÛ
¹ÚÅ׸®¾Æ´Â ¹ÙÀÌ·¯½º, ÆÄÁö, ÇÃ¶ó½º¹Ìµå µîÀÇ Ä§ÀÔÀ» °ßµ®³»±â À§Çؼ ´Ù¾çÇÑ Àü·«µéÀ» »ç¿ëÇØ¿Ô´Ù. ±×Áß CRISPR/Cas ½Ã½ºÅÛ (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins)Àº ncRNA¸¦ ±â¹ÝÀ¸·Î ÇÑ ¹æ¾î½Ã½ºÅÛÀÌ´Ù (Barrangou and Horvath, 2012; Makarova et al., 2011; Westra et al., 2012). CRISPR À¯ÀüÀÚ ÀÚ¸®´Â ¸¹°Ô´Â ¼ö¹é°³ÀÇ °£°Ý ¶ç¿ì°Ô ¿°±â¼¿µé (spacer sequences)ÀÌ ¹Ýº¹¼¿ (repeat sequence) »çÀÌ·Î ±ÔÄ¢ÀûÀ¸·Î ¹è¿µÇ¾î Àִ Ư¼ºÀ» º¸ÀδÙ. CRISPR ¿µ¿ª¿¡¼ Àü»çµÈ ¼±±¸ crRNA´Â °¡°øµÇ¾î¼ ¿Ï¼ºµÈ crRNA°¡ µÇ°í, ÁøÇà»ý¹°ÀÇ RNAi ½Ã½ºÅÛ°ú À¯»çÇÑ ¹æ½ÄÀ¸·Î Cas ´Ü¹éÁúµé°ú ÇÔ²² ¿ÜºÎ¿¡¼ À¯·¡ÇÑ RNA ¶Ç´Â DNA¸¦ Àý´ÜÇÑ´Ù. CRISPR/Cas ½Ã½ºÅÛÀº °í¼¼±Õ·ù¿¡¼´Â Ç×»ó Áö¼ÓÀûÀ¸·Î ¹ßÇöµÇ°í ÀÖÀ¸³ª (Hale et al., 2008; Tang et al., 2002), ƯÁ¤ ½ÅÈ£¿¡ ÀÇÁ¸ÀûÀÎ °æ¿ìµµ ¸¹´Ù. Thermus thermophilusÀÇ CRISPR/Cas Àü»çü´Â ÆÄÁö¿¡ °¨¿°µÈ ÈÄ¿¡ ¹ßÇöÀÌ Áõ°¡µÇ°í, ´ëÀå±Õ¿¡¼´Â H-NS¿¡ ÀÇÇØ casAÀÇ ¹ßÇöÀÌ Á¶ÀýµÇ°í Àֱ⵵ ÇÏ´Ù (Pul et al., 2010). ¼¼Æ÷¸· ½ºÆ®·¹½º¿¡¼ À¯µµµÇ´Â BaeSR 2°³-ÀÎÀÚ Á¶Àý½Ã½ºÅÛ¿¡ ÀÇÇؼ CRISPR/Cas ¹ßÇöÀ» ÃËÁø½ÃÅ°´Â °æ¿ìµµ º¸°íµÇ¾ú´Ù (Perez-Rodriguez et al., 2011). ¾î¶² ´Ù¸¥ ½ºÆ®·¹½ºµéÀÌ CRISPR/Cas ½Ã½ºÅÛÀÇ ¹ßÇöÁ¶Àý°ú ¾î¶² ±âÀÛÀ¸·Î ¿¬°áµÇ¾îÀÖ´ÂÁö ¾ÆÁ÷ ¹àÇôÁöÁö ¾Ê¾ÒÁö¸¸, ¾ÕÀ¸·Î ½ºÆ®·¹½º¿Í CRISPR/Cas ¹ßÇö»çÀÌ¿¡ ¸¹Àº ¿¬°üÀÌ ¹àÇôÁú °ÍÀ¸·Î ±â´ëµÈ´Ù.
9. °íÂû
ÃÖ±Ù ncRNA ¿¬±¸ºÐ¾ßÀÇ ¼º°úµéÀº ½ºÆ®·¹½º Á¶Àý°ú ¹ÚÅ׸®¾Æ º´¿ø¼º µî¿¡ ncRNA°¡ ¾î¶»°Ô °ü¿©ÇÏ°í ÀÖ´ÂÁö¸¦ ÁüÀÛÄÉ ÇÑ´Ù. RNA ¿Âµµ°è, ½Ã½º ¶Ç´Â Æ®·£½º·Î ÄÚµåµÇ´Â ncRNA ¹× CRISPR µîÀº ´Ù¾çÇÑ ½ºÆ®·¹½º¿¡ ´ëÀÀÇÏ¿© ±¸Á¶ÀûÀ¸·Î º¯ÈµÇ°Å³ª, Ÿ°Ù mRNA·Î ºÎÅÍ ¹ßÇö ¶Ç´Â ´Ü¹éÁúÀÇ È°¼ºÀ» Á¶ÀýÇÑ´Ù. ncRNA¸¦ È°¿ëÇÑ ½ºÆ®·¹½ºÀÇ ´ëÀÀÀº ´Ü¹éÁú Àü»çÀÎÀÚ¸¦ ÀÌ¿ëÇÑ ½ºÆ®·¹½º ´ëÀÀ°ú ºñ±³µÇ´Â Á¡µéÀÌ ÀÖ´Ù. ncRNA´Â ª°í ´Ü¹éÁú·Î ¹ø¿ªµÇÁö ¾Ê±â ¶§¹®¿¡ ¼¼Æ÷³» ¿¡³ÊÁö ¼Ò¸ð°¡ Àû°í, ÇÕ¼º°ú ºÐÇØ°¡ ºü¸£´Ù. ¶ÇÇÑ ncRNAµéÀº Àü»çÈÄ ´Ü°è¿¡¼ Ÿ°ÙµéÀ» Á¶ÀýÇÏ´Â °æ¿ì°¡ ¸¹¾Æ¼ ½ºÆ®·¹½º ´ëÀÀ¿¡ ´õ ½Å¼ÓÇÒ ¼ö ÀÖ´Ù. ¶ÇÇÑ ncRNAµéÀº Ãß°¡ÀûÀÎ Á¶Àý´Ü°è¸¦ °®°Ô ÇÏ´Â ±â´Éµµ ÇÑ´Ù. ncRNA¿Í Àü»çÀÎÀڴܹéÁúÀÌ ¸ðµÎ °ü¿©ÇÏ´Â Á¶Àý½Ã½ºÅÛÀÇ °æ¿ì ¹ßÇöÀÇ ´©¼ö°¡ ÃÖ¼ÒÈµÇ°í µ¿¿ªÇÐÀûÀ¸·Îµµ Àü»çÀÎÀÚ Çϳª¸¸ »ç¿ëÇÏ´Â °Íº¸´Ù ÀåÁ¡ÀÌ ¸¹´Ù (Levine and Hwa 2008).
´ë¿ë·® ½ÇÇè±â¼ú°ú, »ý¹°Á¤º¸ÇÐÀû ±â¹ýµéÀÇ ¹ß´Þ°ú ÇÔ²² ¹ÚÅ׸®¾Æ ½ºÆ®·¹½ºÁ¶Àý¿¡ °ü¿©ÇÏ´Â ´Ù¾çÇÑ ncRNAµéÀÌ ´õ ¸¹ÀÌ ¹ß°ßµÉ °ÍÀ¸·Î º¸ÀδÙ. ¾à¹° À¯»çü¿¡ ´ëÇÑ ¸®º¸½ºÀ§Ä¡¸¦ È°¿ëÇÏ¿© Áã¿¡¼ S. aureusÀÇ º´¿ø¼ºÀ» °¨¼Ò½ÃÅ°°Å³ª (Mulhbacher et al., 2010), Cas9°ú ÇÕ¼º °¡À̵å ncRNA¸¦ ÀÌ¿ëÇÑ CRISPR ½Ã½ºÅÛÀ» ¿°»öü Á¶ÀÛ¿¡ È°¿ëÇϰųª (Cong et al., 2013; Jinek et al., 2012; Mali et al., 2013)ÇÏ´Â »õ·Î¿î ±â¼úµé·Îµµ ¸¹ÀÌ Àû¿ëµÇ°í ÀÖ´Ù. ´õ ³ª¾Æ°¡ ncRNA¸¦ Áø´Ü ¸¶Ä¿³ª ¾à¹° Ÿ°ÙÀ¸·Î ÇÏ¿© ¹ÚÅ׸®¾ÆÀÇ º´¿ø¼ºÀ» Á¶ÀýÇÏ´Â ¿¬±¸°¡ »õ·Î¿î µµÀüÀÌ µÉ °ÍÀ¸·Î »ý°¢µÈ´Ù.
Âü°í¹®Çå
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