Regulation of RNA decay and cellular function by 3′-5′ exoribonuclease DIS3L2

Figures & data

Table 1. DIS3L2-mediated RNA decay and corresponding biological function it impacts.

Type	Targets	TUTases	Cellular function	References
microRNA	pre-let-7	TUT4/TUT7	Differentiation of ESCs	[3]
	pre-let-7	TUT4/TUT7	Differentiation of ESCs	[4]
	miR-27	TUT1	N/A	[16]
	pre-miR-9	poly(U)-independent	Neuronal differentiation	[21]
mRNA	ARE-containing mRNAs	N/A	N/A	[2]
	mRNA	TUT4/TUT7	Apoptosis	[17]
	mRNA and poly(A) ncRNA	TUT4/TUT7	Apoptosis	[22]
Other ncRNA	Rmrp, 7SL, U1 and U2 snRNA, several snoRNAs, 5s rRNA	TUT4/TUT7	Quality-control for ncRNAs	[18]
	snRNAs, vault RNAs, Y RNAs, BC200 RNA, FTL_short RNA	TUT4/TUT7	Surveillance of maturing snRNA	[19]
	tRNAs, TSSas, rRNAs, snoRNAs,vault RNAs, Y RNAs, snRNAs	TUT4/TUT7	Surveillanceof cytoplasmic RNA	[20]

Figure 1. Structure of human DIS3L2. Human DIS3L2 contains two CSD domains (CSD1, CSD2), one RNB domain, and one S1 domain. Both the CSD domain and the S1 domain are RNA binding domains. The RNB domain provides 3ʹ-5ʹ exoribonuclease activity and the aspartic acid at position 391 (D391) is a catalytic site, whose mutation leads to inhibition of DIS3L2’s exoribonuclease activity.

Figure 2. Function of DIS3L2 during cancer progression. (a) DIS3L2 suppresses the expression of cyclin D1 but enhances the expression of p27 and p21, therefore promoting the cell cycle progression and functioning as an inhibitor during cancer progression. (b) DIS3L2 promotes lin28-mediated suppression of pre-let-7, results in reduced let-7 biogenesis, and facilitates cancer progression.

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