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8.3:

RNA ์•ˆ์ •์„ฑ

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RNA Stability

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– [๊ฐ•์‚ฌ] RNA๋Š” ์ด๋™์„ฑ์ด ์žˆ๋Š”๋น„๊ต์  ์ˆ˜๋ช…์ด ์งง์€ ๋ถ„์ž๋กœDNA๋ณด๋‹ค ๊ตฌ์กฐ์  ํ™”ํ•™์ ์œผ๋กœ ์•ˆ์ •์„ฑ์ด ํ›จ์”ฌ ๋‚ฎ์Šต๋‹ˆ๋‹คRNA์—์„œ, 5 ํƒ„์†Œ ๋‹น ๋ฆฌ๋ณด์Šค๋Š”๋‘ ๋ฒˆ์งธ ํƒ„์†Œ์— ์ˆ˜์‚ฐํ™”๊ธฐ ๊ทธ๋ฃน์ด ์žˆ์ง€๋งŒ๋ฐ˜๋ฉด ๋ฐ์˜ฅ์‹œ๋ฆฌ๋ณด์Šค๋Š” ํ•˜๋‚˜์˜ ์ˆ˜์†Œ๋ฅผ ๊ฐ€์ง€๊ณ  ์žˆ์Šต๋‹ˆ๋‹คํ•˜์ด๋“œ๋ก์‹ค ๊ทธ๋ฃน์˜ ์ˆ˜์†Œ๋Š”๊ธฐ์ดˆ ์šฉ์•ก์—์„œ ์ œ๊ฑฐ๋˜๊ธฐ ์‰ฝ์Šต๋‹ˆ๋‹ค์ด๋ ‡๊ฒŒ ๋˜๋ฉด ๋‚จ์•„ ์žˆ๋Š” ์Œ์ „ํ•˜๋ฅผ ๋ค ์‚ฐ์†Œ๋Š”์ธ์‚ฐ์—ผ ๋‹น์‹ฌ์„ ๊นจํŠธ๋ฆด ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค๊ฒŒ๋‹ค๊ฐ€ RNA๋Š” ๋Œ€๊ฐœ ๋‹จ์ผ ๊ฐ€๋‹ฅ์ด๊ธฐ ๋•Œ๋ฌธ์—DNA์˜ ์ด์ค‘๋‚˜์„ ๋ณด๋‹ค ๊ตฌ์กฐ์ ์œผ๋กœ์•ˆ์ •์„ฑ์ด ๋–จ์–ด์ง‘๋‹ˆ๋‹ค๋˜ํ•œ RNA ๋ถ„์ž๋Š” DNA ๋ถ„์ž๋ณด๋‹ค ํ›จ์”ฌ ์งง๊ธฐ ๋•Œ๋ฌธ์—๋๋ถ€๋ถ„์—์„œ ์•ˆ์ •์„ฑ์ด ๋” ์ €ํ•˜๋˜์ฃ ์™ธ๋ถ€ ์š”์ธ๋„ RNA์˜ ์•ˆ์ •์„ฑ์— ์˜ํ–ฅ์„ ๋ฏธ์น  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค์˜ˆ๋ฅผ ๋“ค์–ด, RNases๋ผ๊ณ  ๋ถˆ๋ฆฌ๋Š” ์„ธํฌ์งˆ ๋‚ด์˜ํŠน์ • ์—‘์†Œ ๋‰ดํด๋ ˆ์ด์Šค๋Š” ์œ ์ „ ์ •๋ณด๊ฐ€ ํ™œ๋ฐœํ•˜๊ฒŒ๋ฌด๋ฒˆ์—ญ RNA๋ฅผ ๋ถ„ํ•ดํ•ฉ๋‹ˆ๋‹คRNA ๊ฒฐํ•ฉ ๋‹จ๋ฐฑ์งˆ๋กœ ์•Œ๋ ค์ง„ ๋‹ค๋ฅธ ๋‹จ๋ฐฑ์งˆ๋“ค์€์•ˆ์ •์„ฑ์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š”๋ฐ์š”ํŠน์ • RNA ๋‰ดํด๋ ˆ์˜คํƒ€์ด๋“œ ์ˆœ์„œ๋ฅผ ์ธ์‹ํ•˜๊ณ  ๊ฒฐํ•ฉํ•จ์œผ๋กœ์จ ๋ง์ž…๋‹ˆ๋‹คAU๊ฐ€ ํ’๋ถ€ํ•œ ์š”์†Œ๋ฅผ ๊ฐ€์ง„ ์ฆ‰ ๋ณดํ†ต AUUUA ํ˜•ํƒœ๋กœ ๋ฐ˜๋ณต๋˜๋Š”mRNA ์ „์‚ฌ๋ฌผ ๊ตฌ๊ฐ„์€3ํ”„๋ผ์ž„ ๋ฌด๋ฒˆ์—ญ ๊ตฌ์—ญ ์ฆ‰ 3-ํ”„๋ผ์ž„ UTR์—์„œ์„œ๋กœ ๋Œ€๋ฆฝ ์Œ ์—ญํ• ์„ ๊ฐ€์ง€๋Š”๋‹ค๋ฅธ ์ข…๋ฅ˜์˜ RNA ๊ฒฐํ•ฉ ๋‹จ๋ฐฑ์งˆ์„ ๋Œ์–ด๋“ค์ž…๋‹ˆ๋‹ค์ด ๋‹จ๋ฐฑ์งˆ ์ค‘ ์ผ๋ถ€๋Š” mRNA์˜ ์•ˆ์ •์„ฑ์„ ํ–ฅ์ƒํ•˜๋ฉฐ3-ํ”„๋ผ์ž„ UTR๋กœ ์ œํ•œ๋˜๋Š” ๋™์•ˆ๋‹จ๋ฐฑ์งˆ ์œ ์ „ ์ •๋ณด ๋ฒˆ์—ญ์„ ์ฆ๊ฐ€์‹œํ‚ค๋Š” ๋ฐ˜๋ฉด ๋‹ค๋ฅธ ๋ถ€๋ถ„์—์„œ๋Š”๋น ๋ฅด๊ฒŒ ์„ฑ๋Šฅ ์ €ํ•˜๋˜๋„๋ก ํ•ด๋‹น ์ „์‚ฌ์ฒด๋ฅผ ๋ถˆ์•ˆ์ •ํ•˜๊ฒŒ ํ•ฉ๋‹ˆ๋‹ค๋”ฐ๋ผ์„œ, RNA ๋ถ„์ž๊ฐ€ ๋ณ€ํ™˜์—์‚ฌ์šฉํ•  ์ˆ˜ ์žˆ๋Š” ์‹œ๊ฐ„์€ ๊ฐ€๋ณ€์ ์ด๋ฉฐ์—ฌ๋Ÿฌ ์š”์ธ์— ๋”ฐ๋ผ ๋‹ฌ๋ผ์ง‘๋‹ˆ๋‹ค

8.3:

RNA ์•ˆ์ •์„ฑ

์˜จ์ „ํ•œ DNA ๊ฐ€๋‹ฅ์€ ํ™”์„์—์„œ๋„ ๋ฐœ๊ฒฌ๋  ์ˆ˜ ์žˆ์ง€๋งŒ, RNA๋Š” ๋•Œ๋•Œ๋กœ ์‹คํ—˜์‹ค ์กฐ๊ฑด ์•„๋ž˜์—์„œ๋„ ์˜จ์ „ํžˆ ์œ ์ง€ํ•˜๊ธฐ ํž˜๋“ค์–ด ๊ณผํ•™์ž๋“ค์ด ๊ณ ๊ตฐ๋ถ„ํˆฌํ•ฉ๋‹ˆ๋‹ค. ์ด์™€ ๊ฐ™์€ ์•ˆ์ •์„ฑ(stability)๊ณผ ์ง€์†์„ฑ(longevity)์˜ ์ฐจ์ด๋Š” RNA์™€ DNA ์‚ฌ์ด์˜ ๊ตฌ์กฐ์  ์ฐจ์ด์—์„œ ์˜ต๋‹ˆ๋‹ค. DNA๋Š” ์ด์ค‘ ๊ฐ€๋‹ฅ์ด๊ธฐ ๋•Œ๋ฌธ์— ๋ณธ์งˆ์ ์œผ๋กœ ๋” ์•ˆ์ •์ ์ž…๋‹ˆ๋‹ค. RNA๋Š” ๋‹จ์ผ ๊ฐ€๋‹ฅ์ด๋ผ ๋œ ์•ˆ์ •์ ์ž…๋‹ˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋” ์œ ์—ฐํ•˜๋ฉฐ ์•ฝํ•œ ๋‚ด๋ถ€ ๊ฒฐํ•ฉ์„ ํ˜•์„ฑํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ, ๋Œ€๋ถ€๋ถ„์˜ ์„ธํฌ ๋‚ด RNA๋Š” ์ƒ๋Œ€์ ์œผ๋กœ ์งง์€ ๋ฐ˜๋ฉด, DNA๋Š” 2์–ต 5์ฒœ๋งŒ ๋‰ดํด๋ ˆ์˜คํƒ€์ด๋“œ(nucleotide) ๊ธธ์ด๊นŒ์ง€ ๊ธธ ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. RNA๋Š” ๋ฆฌ๋ณด์Šค(ribose) ์„คํƒ•์˜ ๋‘ ๋ฒˆ์งธ ํƒ„์†Œ์— ์ˆ˜์‚ฐ๊ธฐ(hydroxyl group)๋ฅผ ๊ฐ€์ง€๊ณ  ์žˆ์–ด ๋‹น-์ธ์‚ฐ ๋ผˆ๋Œ€์˜ ํŒŒ์† ๊ฐ€๋Šฅ์„ฑ์„ ๋†’์ž…๋‹ˆ๋‹ค.

์„ธํฌ๋Š” RNA์˜ ๋ถˆ์•ˆ์ •์„ฑ์„ ์ด์šฉํ•˜์—ฌ ์ง€์†์„ฑ๊ณผ ๊ฐ€์šฉ์„ฑ์„ ๋ชจ๋‘ ์กฐ์ ˆํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ๋ณด๋‹ค ์•ˆ์ •์ ์ธ mRNA๋Š” ๋œ ์•ˆ์ •์ ์ธ mRNA ์ „์‚ฌ๋ฌผ(transcript)๋ณด๋‹ค ๋” ์˜ค๋žœ ์‹œ๊ฐ„ ๋™์•ˆ ๋ฒˆ์—ญ(translation)์ด ๊ฐ€๋Šฅํ•ฉ๋‹ˆ๋‹ค. ์„ธํฌ ๋‚ด RNA ๊ฒฐํ•ฉ ๋‹จ๋ฐฑ์งˆ(RNA binding protein, ์ค„์—ฌ์„œ RBP)์€ RNA ์•ˆ์ •์„ฑ์„ ์กฐ์ ˆํ•˜๋Š” ๋ฐ ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•ฉ๋‹ˆ๋‹ค. RBP๋Š” mRNA์˜ 3’’ ๋น„๋ฒˆ์—ญ์ง€์—ญ(untranslated region, ์ค„์—ฌ์„œ UTR; ๋น„๋ฒˆ์—ญ๋ถ€์œ„)์— ์žˆ๋Š” ํŠน์ • ์„œ์—ด(AUUA)์— ๊ฒฐํ•ฉํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ํฅ๋ฏธ๋กญ๊ฒŒ๋„, AUUA์˜ ๋ฐ˜๋ณต ํšŸ์ˆ˜๊ฐ€ ์ ์œผ๋ฉด ์•ˆ์ •ํ™” RBP๊ฐ€ ๋œ ๋ชจ์ง‘๋˜๋Š” ๊ฒƒ์œผ๋กœ ๋ฏธ๋ฃจ์–ด๋ณด์•„ AUUA์˜ ๋ฐ˜๋ณต ํšŸ์ˆ˜๋Š” ํŠน์ •ํ•œ ๋ฐฉ์‹์œผ๋กœ RBP๋ฅผ ๋ชจ์ง‘ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์ž…๋‹ˆ๋‹ค. ๋˜ํ•œ, ์—ฌ๋Ÿฌ ๋ฒˆ ๊ฒน์น˜๋Š” AUUA ๋ฐ˜๋ณต์€ ๋ถˆ์•ˆ์ •ํ™” RBP์˜ ๊ฒฐํ•ฉ์„ ๋ถˆ๋Ÿฌ์˜ต๋‹ˆ๋‹ค. ๋ชจ๋“  ์„ธํฌ์—๋Š” RNA๋ฅผ ๋ถ„ํ•ดํ•˜๋Š” RNase(ribonuclease; ๋ฆฌ๋ณดํ•ต์‚ฐ๊ฐ€์ˆ˜๋ถ„ํ•ดํšจ์†Œ)๋ผ๊ณ  ๋ถˆ๋ฆฌ๋Š” ํšจ์†Œ๊ฐ€ ์žˆ์Šต๋‹ˆ๋‹ค. ์ผ๋ฐ˜์ ์œผ๋กœ 5’์บก(5’cap)๊ณผ ํด๋ฆฌ A ๊ผฌ๋ฆฌ(poly A tail)๋Š” ์„ธํฌ์— ๋” ์ด์ƒ ์ „์‚ฌ๋ฌผ์ด ํ•„์š”ํ•˜์ง€ ์•Š์„ ๋•Œ๊นŒ์ง€ ์ง„ํ•ต์ƒ๋ฌผ mRNA๋ฅผ ๋ถ„ํ•ด๋กœ๋ถ€ํ„ฐ ๋ณดํ˜ธํ•ฉ๋‹ˆ๋‹ค.

์š”์ฆ˜ ๋– ์˜ค๋ฅด๋Š” ํ›„์„ฑ์ „์‚ฌ์ฒดํ•™(epitranscriptomics) ์—ฐ๊ตฌ๋Š” ์กฐ์ ˆ mRNA ๋ณ€ํ˜•(regulatory mRNA modification)์„ ์ •์˜ํ•˜๋Š” ๊ฒƒ์„ ๋ชฉํ‘œ๋กœ ํ•˜๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ๊ณผํ•™์ž๋“ค์€ ์ตœ๊ทผ ๋ฉ”ํ‹ธํ™”(methylation)๊ฐ€ mRNA ์•ˆ์ •์„ฑ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ๋ฐœ๊ฒฌํ–ˆ์Šต๋‹ˆ๋‹ค. ์•„๋ฐ๋…ธ์‹ (adenosine) ์ž”๊ธฐ(residue)์˜ ๋ฉ”ํ‹ธํ™”(m6A)๋Š” mRNA ๋ฒˆ์—ญ๊ณผ ๋ถ„ํ•ด๋ฅผ ์ฆ๊ฐ€์‹œํ‚ค๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์ž…๋‹ˆ๋‹ค. ๋˜ํ•œ m6A๋Š” ์ŠคํŠธ๋ ˆ์Šค ๋ฐ˜์‘, ํ•ต์™ธ ์ˆ˜์†ก(nuclear export), mRNA ์„ฑ์ˆ™(mRNA maturation)์—๋„ ์—ญํ• ์„ ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์ž…๋‹ˆ๋‹ค. ๋ณ€ํ˜•๋œ ์œ ๋ผ์‹ค(uracil) ์ž”๊ธฐ์ธ ์ˆ˜๋„์œ ๋ฆฌ๋”˜(pseudouridine)์˜ ์กด์žฌ ๋˜ํ•œ RNA ์กฐ์ ˆ์— ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์ž…๋‹ˆ๋‹ค.

Suggested Reading

Zhao, Boxuan Simen, Ian A. Roundtree, and Chuan He. “Post-Transcriptional Gene Regulation by MRNA Modifications.” Nature Reviews. Molecular Cell Biology 18, no. 1 (January 2017): 31–42. [Source]

Agris, Paul F. “The Importance of Being Modified: An Unrealized Code to RNA Structure and Function.” RNA 21, no. 4 (April 2015): 552–54. [Source]